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Archive for the ‘Immune System’ Category

Collaboration to chart AI-generated map of the immune system –

Saturday, December 26th, 2020

Immunai, a company specializing in comprehensive mapping of the human immune system, is joining forces with 10x Genomics. The latter will leverage its single-cell technologies to map hundreds of cell types and states. By applying its artificial intelligence (AI) and machine learning (ML) algorithms, Immunai supports biomarker discovery and insight generation to help power new therapeutic discoveries and accelerate drug development.

Outsourcing-Pharma (OSP) discussed the partnership with Luis Voloch (LV), CTO and co-founder of Immunai, and how the map generated through the collaborative effort stands to benefit drug developers.

OSP: Please tell us a bit about Immunai.

LV: Immunai is comprehensively mapping the immune system to power new therapeutic discoveries, accelerate drug development, and improve patient outcomes. Leveraging single-cell technologies to profile cells and machine learning to map incoming data to hundreds of cell types and states, Immunai supports biomarker discovery and insight generation to better detect, diagnose, and treat disease.

The immune system is an incredibly complex, distributed system that researchers have been trying to understand with limited success for years. Immunai is the first company to fully map the immune system, generating the largest proprietary database for immunology.

Were disrupting legacy companies by analyzing 10,000 times more data from each cell than they are. No one is doing exactly what were doing.

OSP: How did you come to partner with 10x Genomics?

LV: There is an undeniable fit between the goals and capabilities of our two companies. At Immunai, we want to use AI to identify and understand novel elements within hundreds of different cell types to inform drug development, and we have been leveraging 10xs products to do that at a granular level from the start.

Through our initial work together, we identified even more mutually beneficial applications of our technologies for pharma companies and academic institutions alike. So we most recently applied to 10xs Certified Service Provider Program to give 10xs customers access to our advanced immune profiling solutions.

OSP: What does each of you bring to the table in this partnership, and how will the collaboration work?

LV: With this collaboration, we will pair our immune cell atlas with the phenotypic clinical data that hospitals, biopharma, and biotech companies derive from 10xs technology. With Immunais end-to-end computational AI pipeline customized for single-cell methods, researchers at pharmaceutical and cell therapy companies can better understand how immune cells operate with both granularity and scale. In turn, we will help 10xs customers answer clinical and translational questions related to the immune response to therapies.

OSP: Could you please talk a bit about the evolution of AI and how drug discovery professionals have made use of it to date?

LV: An analysis published earlier this year in the Journal of the American Medical Association found that the median cost of R&D for a new drug in the years between 2009 and 2018 was $985 million. This ever-increasing cost forces pharma companies to search for innovative means to create efficiencies in drug development.

Pharma companies are catching on to what Immunai already knows: AI can maximize our ability to layer data points, uncover deep insights, and advance research.

We envision AIin conjunction with human intelligenceas the major component to understanding and curing cancer. AI will increasingly have a tremendous impact on pharma. Pharma has traditionally had to experiment by testing out different compounds in a dish or in animals.

With more biological data available, AI provides a partial alternative to this that allows us to predict (without actual experiments) the impact of compounds in different biological systems. This ability has increased the speed in which we can profile and improve compounds.

OSP: What is particularly novel and noteworthy about this projectwhat do you hope to accomplish that hasnt been accomplished before?

LV: Until now, no one has been able to uncover the complexities of the immune system in the way that Immunai has. Current single-cell approaches generally operate at the scale of small academic studies because they suffer from the problem of batch effects, where noise from variation in biological samples quickly washes out any real biological signal as scale grows.

Immunais end-to-end platform is designed to manage batch effects through both proprietary lab methods and advanced AI, allowing us to build a large multi-omic single-cell database that we pair with clinical context. We train our proprietary neural network models on this data to surface insights about immune responses and facilitate the development of better therapies.

This lack of understanding of the immune system contributes to inefficiencies in drug R&D. Developing immunotherapies based on information provided by only two cells doesnt give researchers a view of the entire picture.

We believe that this collaboration will help to drastically improve the development of therapies and answer some of the biggest questions about cancer.

OSP: Is there anything youd like to add that we didnt touch upon?

LV: Our work with 10x is the second official collaboration weve announced over the past few months. In November, we announced a collaboration with Baylor College of Medicine to drive forward the development of novel NKT cell therapies. As our database continues to grow with these partnerships, we can apply learnings around immune response across different diseases from cancer to autoimmune disorders to cardiovascular diseases as well.

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Immunity Against COVID-19 Post Recovery May Last for At Least 8 Months, Suggests New Study | The Weather Channel – Articles from The Weather Channel |…

Saturday, December 26th, 2020

Representative Image

As a majority of the world collectively holds its breath waiting for COVID-19 vaccinations, indirect protective measures such as social distancing and wearing of masks have been keeping people out of the coronavirus' grasp. Furthermore, the development of antibodies in individuals that have successfully beaten the virus has also served as an 'antivirus' protection for themselves and those around them.

But with that said, there has been constant speculation on just how long these antibodies and the overall immunity against COVID-19 lasts in the human system. The clouds of mystery pertaining to this particular question continue to govern scientists, virologists, and researchers. Thus far, several studies have suggested that the antibodies against the infection may wane in just a few months after recovery, thereby raising concerns of contracting the infection more than once.

Now, a team of scientists from the Monash University in Australia has given the world a Christmas gift through their new study, which has indicated that immunity against COVID-19 can last for at least eight months. The research is all the more significant at the moment, when vaccines are still in their rollout phases.

"This has been a black cloud hanging over the potential protection that could be provided by any COVID-19 vaccine, and gives real hope that once a vaccine or vaccines are developed, they will provide long-term protection," said immunologist Menno van Zelm from Monash University.

The new study specifically took into account a type of cells in our immune system known as the memory B cells or MBC. These cells function to remember any infection that the human body contracts after being invaded by a pathogen, say virus. Therefore, if an individual contracts the virus again, MBC functions to trigger a protective immune response through its memory, and thus shields an individual from re-infection.

To understand the presence of memory cells, the team chased two main components of the SARS-CoV-2 virusthe spike and the nucleocapsid proteins. The study noted that the memory B cells were rapidly generated in all the patients following the infection, and remained detectable after 240 days. This very extended presence of the memory cells showcases a long-term immune response to COVID-19. It also highlights the fact that a patients immune system has the ability to fight when re-exposed to the pathogen by the rapid production of antibodies.

"These results are important because they show, definitively, that patients infected with the COVID-19 virus do in fact retain immunity against the virus and the disease," said Dr van Zelm.

Representative Image

Interestingly, the study also ascertained that even after months of virus spread, during which millions of positive infections have been found, there have not been many reported cases of re-infections among the population across the globe.

A similar study was recently published in the journal Emerging Infectious Diseases, which also confirmed the presence of antibodies against SARS-CoV-2 after 8 months of infection in most asymptomatic or mildly symptomatic patients. The study was conducted using the immunoassays test on 58 positive patients.

When attacked by a pathogen, our immune system produces proteins called antibodies in order to fight the infection. If the infected person can produce sufficient antibodies, he can recover from the disease caused by that pathogen.

To examine how long these antibodies last in case of COVID-19, researchers monitored about 25 people diagnosed with different severities of the disease, and then collected post-infection blood samples from themstarting from day 4 to day 242 after recovery. On the other hand, they also obtained data from 36 healthy control patients between March to September, so as to compare each patient's antibody presence and levels of virus-specific immune cells.

After examining this long period data, the researchers noted that the antibodies against COVID-19especially immunoglobulin (IgG), which is the most common antibody in the human bodystarted to fade in just 20 days post-infection, just like the previous studies had suggested.

Earlier, a similar research conducted by the Chongqing Medical University in China had also suggested that people who have recovered from COVID-19 showcased a sharp decline of up to 90% in their Immunoglobulin (IgG) antibodies within the time frame of 2-3 months.

The new research is a collaborative work between Monash University, The Alfred Hospital, and the Burnet Institute in Melbourne. The study was published in the journal Science Immunology on December 22, and can be accessed here.


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Immunity Against COVID-19 Post Recovery May Last for At Least 8 Months, Suggests New Study | The Weather Channel - Articles from The Weather Channel |...


Thats a sign your immune system is working: Side effects are normal with COVID-19 vaccines – KX NEWS

Saturday, December 26th, 2020

With the roll out of COVID-19 vaccines, many people may have questions about side effects.

During the clinical trials, people who were administered the Moderna or Pfizer vaccine experienced fever, joint pain and redness around the injection site.

These symptoms are said to last one to two days after receiving the dosage.

We spoke with a North Dakota Department of Health consultant who says the side effects are normal and a sign that your immune system is reacting to the vaccine.

Its more common to see these side effects after you receive the second dose of the vaccine. So dont be surprised if after the first dose you may have minimal or very few side effects, but after the second dose if that fever or those body aches are slightly more prominent again thats a sign your immune system is working, said Kylie Hall.

Hall says during the clinical trial side effects were more common in the Moderna vaccine than the Pfizer.

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Thats a sign your immune system is working: Side effects are normal with COVID-19 vaccines - KX NEWS


What is the role of nutrition in immunity and host susceptibility to COVID-19? – Gut Microbiota for Health

Saturday, December 26th, 2020

Immune system activity is enhanced after a viral infection such as COVID-19

Although the immune system is always working to prevent pathogens from invading the body, as well as eliminating those pathogens and generating an immunological memory, the metabolic activity of immune cell types is enhanced following a viral infection such as COVID-19. That heightened activity is accompanied by a higher demand of energy and nutrients, which come from diet, to meet the immune cells requirements.

In a new comprehensive review, Prof. Philip Calder from the University of Southampton provides an update on the role of nutrition in supporting the immune system as part of the current fight against COVID-19.

Different levels of evidence have shown the following as key nutrients involved in reducing infection risk by supporting antibacterial and antiviral defense:

The mechanisms by which each of the nutrients named above support the immune system include the strengthening of innate immune responses and antioxidant systems. Likewise, the gut microbiome also plays a role through its involvement in training the immune system and avoiding excessive inflammatory responses to pathogenic organisms. Furthermore, it has been shown to be altered in patients with COVID-19.

Although zinc and selenium have been shown to be particularly relevant for supporting antiviral defense, there is no single nutrient or diet that will prevent people getting infected with SARS-CoV-2 or have an impact on mortality in COVID-19. The immune system plays a central role in protecting against infection, but due to its complexity and the multiple ways in which it deals with viruses, the best advice is to consume a healthy, diverse and well-balanced diet that will provide the nutrients required to achieve a healthy gut microbiome, which can also benefit the immune system.

Considering that some patients with COVID-19 have been shown to have an altered gut microbiome, coupled with gastrointestinal symptoms, probiotics could be used as means of reducing bacterial translocation and secondary infection. However, even though probiotics containing Lactobacillus and Bifidobacterium have been shown to improve immune function and enhance the response to some vaccinations, it is still early to conclude whether the gut microbiome plays a therapeutic role in preventing or treating COVID-19.

In some COVID-19 patients, an excessive inflammatory reaction (called a cytokine storm) can occur as a compensatory reaction by immune cells for dealing with lung damage. In that regard, Philip Calder acknowledges in the review that the polyunsaturated omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to be relevant in resolving ongoing inflammatory processes in patients with an outbreak of severe acute respiratory distress syndrome.

Although there is no specific evidence that nutrients alone can help protect against or lessen the effects of COVID-19, eating well and keeping a healthy weight will help the immune system cope better with the demands placed on the body before, during and after COVID-19 infection.

The World Health Organization has stressed the importance of a balanced diet to maintain a strong immune system and to avoid or minimize infections during the COVID-19 outbreak. For instance, the WHO has recommended consuming 9 servings of fruit and vegetables per day, which is more than in the usual dietary recommendations.

Although micronutrients, nutraceuticals and probiotics could be of interest for enhancing immunity during the COVID-19 pandemic, it is too early to make specific recommendations due to the small number of intervention studies that have been published.

In particular, patients with malnutrition, diabetes, obesity, cardiovascular disease and respiratory diseaseand especially older peopleare at a higher risk of complications from COVID-19 and will require personalized nutrition advice. In an attempt to provide specific nutritional advice for supporting the proper functioning of the immune system, the International Society for Immunonutrition has suggested increasing the intake of vitamin E, zinc and vitamin C in older people, along with vitamin D if they have a low serum vitamin D status.

So far, the most effective way of limiting the spread of COVID-19 is by preventing contact between people. Although several vaccines have been developed for prevention of SARS CoV-2, mass vaccination roll-out will take months. Meanwhile, nutrition should be considered in any approach to ensure that individuals immune systems are well supported, even though no nutrition studies have been published yet in the context of COVID-19.


Calder PC. Nutrition, immunity and COVID-19. BMJ Nutr Prev Health. 2020; 3(1):74-92. doi: 10.1136/bmjnph-2020-000085.

World Health Organization. Nutrition advice for adults during the COVID-19 outbreak [cited 3 December 2020]. Available from:

Jayawardena R, Sooriyaarachchi P, Chourdakis M, et al. Enhancing immunity in viral infections, with special emphasis on COVID-19: a review. Diabetes Metab Syndr. 2020; 14(4):367-382. doi: 10.1016/j.dsx.2020.04.015.

Derbyshire E, Delange J. COVID-19: is there a role for immunonutrition, particularly in the over 65s? BMJ Nutr Prev Health. 2020; 3(1):100-105. doi: 10.1136/bmjnph-2020-000071.

International Society for Immunonutrition. ISIN Position Statement on Nutrition, Immunity and COVID-19. 2020 March [cited 2 December 2020]. In: ISIN [Internet]. Available from:

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What is the role of nutrition in immunity and host susceptibility to COVID-19? - Gut Microbiota for Health


VERIFY: Yes, you will need to wear a mask after you get COVID-19 vaccine –

Saturday, December 26th, 2020

Dr. Dirk Sostman, chief academic officer at Houston Methodist, addressed questions and claims about how the shot and the immune system.

HOUSTON The VERIFY team is working hard to make sure you have the facts before you get vaccinated. Dr. Dirk Sostman, chief academic officer at Houston Methodist, addressed questions and claims about how the shot and the immune system.

CLAIM: I won't need to wear a mask after I get vaccinated for COVID-19.

FALSE. Dr. Sostman said, One of the things we don't know about this vaccine is whether it can prevent you from transmitting the virus to other people. We know itll protect you from getting sick, but you may have an asymptomatic infection and be able to pass on the virus to others. So, you must continue to wear a mask.

CLAIM: Vaccines can overload your immune system.

FALSE. Dr. Sostman said, There is nothing to indicate that vaccines will overload your immune system.

CLAIM: Natural immunity is healthier and more effective than vaccine-induced immunity.

Partly true. Dr. Sostman said, Natural immunity may give you a reaction to a wider range of parts of the virus, which potentially could be good. But, in general, what we found with these vaccines is that they actually produce a stronger immune response than natural immunity.

CLAIM. If everyone around me is immune, then I don't need to be vaccinated.

FALSE. Dr Sostman said, If everyone around you is vaccinated and immune, how do you think they got that way? We all have to be vaccinated and become immune in order for the whole population of the United States to be immune and safe from this virus.

CLAIM: Once you receive the coronavirus vaccine, you are immune for life.

UNKNOWN. Dr. Sostman said, There are reasons to believe you could be immune for a long time, but we have no real data to indicate how long the immunity is going to last.

CLAIM: You don't need both doses of the two-dose vaccine.

FALSE. Dr. Sostman said, You really do need both doses. There is some protection after the first does, but the protection is much better after the second dose. The second dose is probably what is going to give you a longer lasting immune response.

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VERIFY: Yes, you will need to wear a mask after you get COVID-19 vaccine -


Vitamin alternative: Adaptogens offer a new way of boosting the immune system – Las Vegas Sun

Saturday, December 26th, 2020

Supplements, vitamins and other botanicals have been a part of the health and wellness industry for years, and public interest shows no signs of slowing. According to a market research report by Fortune Business Insights, the immune health supplements market is expected to grow $13 billion over the next seven years.

And while health stores have always sold various capsules, powders and tinctures, theres another wave of immune-boosting remedies called adaptogens that are becoming increasingly popular.

Not sure which adaptogenic mushroom is right for you? Keep reading to determine which you should put in your morning potion.

Chaga. This immune-boosting mushroom is packed with antioxidants and is believed to fight inflammation.

Shiitake. According to, shiitake mushrooms are high in natural copper, which might support healthy blood vessels, bones and overall immune system health.

Maitake. Known as the dancing mushroom, maitake is believed to promote mental and physical well-being. Popular for its immune-boosting properties, it is also used to aid in hormonal balance.

Reishi. Similar to chaga, reishi is full of antioxidants but can also help relieve depression. Reishi is also believed to help lower cholesterol and maintain heart health.

Heather Harmon and Jimmy Aston founded local apothecary the Shasta Shop, which opened last year and exists both online and in pop-up form at the Downtown Summerlin Farmers Market every Saturday, as a way to offer the community affordable access to herbs and adaptogens.

Shasta really came out of a love of health and wellnessmental health, physical health, Harmon says. To be healthy and to be thoughtful doesnt necessarily have to be that expensive.

Harmon had suffered a stress-related injury and was taking more than 20 pills and capsules to keep herself feeling healthy. But the price of those supplements started to add up.

I have always lived a really high-stress lifestyle, Harmon says. I was trying to process how [to] deal with the pressure and stress of everyday life and still be healthy and get all the nutrients you need.

I was doing things a bit backward, she continues, taking all these vitamins and running in circles. Thats when I started looking at reishi and chaga [mushrooms] and solutions that have been available to people for centuries.

Harmon and Aston say that instead of taking a daily concoction of vitamins and supplements, you can get similar or better effects from a teaspoon of adaptogens and superfoods in your coffee, tea or morning smoothie.

All adaptogens have a similar foundation of benefits, Aston explains. All of them are loaded with vitamins and nutrients and antioxidants, [but] each one has a special something that stands out more than anything else.

Aston recommends a shiitake or maitake mushroom powder to start. Thats a good all-around adaptogen that helps you in every situation and every part of your life. Its great for mental and physical health, and it has all these vitamins and nutrients. The couple also suggests lions mane, which Aston says has received quite a lot of press during the past few years for its alleged ability to produce new neural pathwayssomething that could potentially help prevent Alzheimers or dementia.

Root and mushroom powders arent all that Shasta has in store. The son of Taiwanese restaurateurs, Aston created his signature eggplant crisps after tweaking a family recipe thats been passed down through generations.

I veganized this recipe from my great-great-great-grandmother and then used it as a marinade for the eggplant, Aston says. Theres only four ingredients. We marinate it for over 24 hours, put it in a dehydrator for another 24 hours and then have these incredible snacks.

We work seasonally, Harmon adds, explaining that Shasta uses fresh fruits and vegetables when theyre available. When persimmons are gone, theyre gone. We dont fight to have something that isnt in line with the natural cycle or order of things.

As Harmon and Aston gear up for winter, theyre excited to offer shungite powder, a rare provision found only in a specific region of Russia. According to, shungite is a black stone from Shunga, a village in Karelia, Russia. The stone is composed of fullerenes, a type of carbon nanostructure that is believed to fight pathogens, bacteria and viruses, as well as shield against electromagnetic frequencies.

Like all adaptogens, however, the benefits of each mushroom, powder or root takes time. It should be noted that theres little long-term research about adaptogens effects on the body over time. As with all other supplements, you should talk to your doctor before adding adaptogens to your diet or routine.

Adaptogens are not something you take once, Harmon says. Theyre about dedication. They definitely gain traction and are a slow build.

Instead of us taking 19 different capsules and supplements, Aston says, we have some coffee or matcha, put in a measured scoop of our lions mane and pine pollen and call it a day.

This story appeared in Las VegasWeekly.

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Vitamin alternative: Adaptogens offer a new way of boosting the immune system - Las Vegas Sun


U.K. variant puts spotlight on immunocompromised patients’ role in the COVID-19 pandemic – Science Magazine

Saturday, December 26th, 2020

Shoppers wear face masks on Regent Street in London on 19 December, the day the U.K. government imposed new restrictions to curb a rapidly spreading new SARS-CoV-2 variant.

By Kai KupferschmidtDec. 23, 2020 , 2:30 PM

Sciences COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

In June, Ravindra Gupta, a virologist at the University of Cambridge, heard about a cancer patient who had come into a local hospital the month before with COVID-19 and was still shedding virus. The patient was being treated for a lymphoma that had relapsed and had been given rituximab, a drug that depletes antibody-producing B cells. That made it hard for him to shake the infection with SARS-CoV-2.

Gupta, who studies how resistance to HIV drugs arises, became interested in the case and helped treat the patient, who died in August, 101 days after his COVID-19 diagnosis, despite being given the antiviral drug remdesivir and two rounds of plasma from recovered patients, which containedantibodies against the virus. When Gupta studied genome sequences from the coronavirus that infected the patient, he discovered that SARS-CoV-2 had acquired several mutations that might have allowed it to elude the antibodies.

Now, his analysis, reported in a preprint on medRxiv earlier this month, has become a crucial puzzle piece for researchers trying to understand the importance of B.1.1.7, the new SARS-CoV-2 variant first found in the United Kingdom. That strain, which appears to spread faster than others, contains one of the mutations that Gupta found, and researchers believe B.1.1.7, too, may have originated in an immunocompromised patient who had a long-running infection. Its a perfectly logical and rational hypothesis, says infectious disease scientist Jeremy Farrar, director of the Wellcome Trust.

Scientists are still trying to figure out the effects of the mutations in B.1.1.7, whose emergence led the U.K. government to tighten coronavirus control measures and other countries in Europe to impose U.K. travel bans. But the new variant, along with research by Gupta and others, has also drawn attention to the potential role in COVID-19 of people with weakened immune systems. If they provide the virus with an opportunity to evolve lineages that spread faster, are more pathogenic, or elude vaccines, these chronic infections are not just dangerous for the patients, but might have the potential to alter the course of the pandemic.

Its still very unclear whether that is the case, but Farrar believes its important to ensure doctors take extra precautions when caring for such people: Until we know for sure, I think, treating those patients under pretty controlled conditions, as we would somebody who has drug resistant tuberculosis, actually makes sense.

Researchers concern mostly focuses on cancer patients being treated for chemotherapy and similar situations. We dont yet know about people who are immunocompromised because of HIV, for instance, Farrar says.

B.1.1.7 attracted scientists attention because it was linked to an outbreak in Englands Kent county that was growing faster than usual. Sequences showed that virus had accumulated a slew of mutations that together caused 17 amino acid changes in the virus proteins, eight of them in the crucial spike protein. Among them are at least three particularly concerning ones.

One is 69-70del, a deletion that Gupta also found in his Cambridge, U.K., patient whose virus seemed to evade the immune system. It leads to the loss of two amino acids in the spike protein. In lab experiments, Gupta found that lentivirus engineered to carry the SARS-CoV-2 spike protein with this deletion was twice as infectious.

The second is N501Y, a mutation that evolutionary biologist Jesse Bloom of the Fred Hutchinson Cancer Research Center has shown to increase how tightly the protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor, its entry point into human cells. The mutation is also present in 501Y.V2, a variant discovered by researchers in South Africa who investigated rapidly growing outbreaks in three coastal provinces. We found that this lineage seems to be spreading much faster, says Tulio de Oliveira, a virologist at the University of KwaZulu-Natal whose work first alerted U.K. scientists to the importance of N501Y. Anytime you see the same mutation being independently selected multiple times, it increases the weight of evidence that that mutation is probably beneficial in some way for the virus, Bloom says.

The third worrisome change is P681H, which alters the site where the spike protein has to be cleaved to enter human cells. It is one of the sites on spike where SARS-CoV-2 differs from SARS-CoV-1, the virus that caused the worldwide outbreak of severe acute respiratory syndrome in 2003, and the change there may allow it to spread more easily. This one is probably as important as N501Y, says Christian Drosten, a virologist at Charit University Hospital in Berlin.

So far, SARS-CoV-2 typically acquires only one to two mutations per month. And B.1.1.7 is back to this pace now, suggesting it doesnt mutate faster normally than other lineages. Thats why scientists believe it may have gone through a lengthy bout of evolution in a chronically infected patient who then transmitted the virus late in their infection. We know this is rare but it can happen, says World Health Organization epidemiologist Maria Van Kerkhove. Stephen Goldstein, a virologist at the University of Utah, agrees. Its simply too many mutations to have accumulated under normal evolutionary circumstances. It suggests an extended period of within-host evolution, he says.

People with a weakened immune system may give the virus this opportunity, as Guptas data show. More evidence comes from a paper published in The New England Journal of Medicine on 3 December that described an immunocompromised patient in Boston infected with SARS-CoV-2 for 154 days before he died. Again, the researchers found several mutations, including N501Y. It suggests that you can get relatively large numbers of mutations happening over a relatively short period of time within an individual patient, says William Hanage of the Harvard T.H. Chan School of Public Health, one of the authors. (In patients who are infected for a few days and then clear the virus, there simply is not enough time for this, he says.) When such patients are given antibody treatments for COVID-19 late in their disease course, there may already be so many variants present that one of them is resistant, Goldstein says.

Its simply too many mutations to have accumulated under normal evolutionary circumstances. It suggests an extended period of within-host evolution.

The question is whether the mutations arising in such patients could also help the virus spread more rapidly. In research published a few years ago, Bloom showed some of the mutations that arose in influenza viruses in immunocompromised patients later spread globally. Its totally possible that whats happening in immunocompromised patients could foreshadow what happens in the future with the pandemic, Bloom says. But adaptations that help a virus outperform other viruses in a patient can also be very different from what a virus needs to better transmit from patient to patient, he says.

U.K. scientists and others were initially cautious about concluding that B.1.1.7s mutations made the virus better at spreading from person to person. But the new variant is rapidly replacing others, says Mge evik, an infectious disease specialist at the University of St.Andrews. We cant really rule out the possibility that seasonality and human behavior explain some of the increase, she says. But it certainly seems like there is something to do with this variant. Drosten says he was initially skeptical, but has become more convinced as well.

But exactly what impact each mutation has is much more difficult to assess than spotting them or showing theyre on the rise, says Seema Lakdawala, a biologist at the University of Pittsburgh. Animal experiments can help show an effect, but they have limitations. Hamsters already transmit SARS-CoV-2 virus rapidly, for instance, which could obscure any effect of the new variant. Ferrets transmit it less efficiently, so a difference may be more easily detectable, Lakdawala says. But does that really translate to humans? I doubt it. A definitive answer may be months off, she predicts.

One hypothesis that scientists are discussing is that the virus has increased how strongly it binds to the ACE2 receptor on human cells, and that this allows it to better infect children than before, expanding its playing field. But the evidence for that is very thin so far, evik says. Even if children turn out to make up a higher proportion of people infected with the new variant, that could be because the variant spread at a time when there was a lockdown but schools were open. Another hypothesis is that P681H helps the virus better infect cells higher up in the respiratory tract, from where it can spread more easily than from deep in the lungs, Drosten says.

One important question is whether the South African or U.K. lineage might lead to more severe disease or even evade vaccine-induced immunity. So far there is little reason to think so. Although some mutations have been shown to let the virus evade monoclonal antibodies, vaccines and natural infections both appear to lead to a broad immune response that targets many parts of the virus, says Shane Crotty of the La Jolla Institute for Immunology. It would be a real challenge for a virus to escape from that. The measles and polio viruses have never learned to escape the vaccines targeting them, he notes: Those are historical examples suggesting not to freak out.

At a press conference yesterday, BioNTech CEO Uur ahin pointed out that the U.K. variant differed in only nine out of more than 1270 amino acids of the spike protein encoded by the messenger RNA in the very effective COVID-19 vaccine his company developed together with Pfizer. Scientifically it is highly likely that the immune response by this vaccine also can deal with the new virus, he said. Experiments are underway that should confirm that in the first week of 2021, ahin added.

Sbastien Calvignac-Spencer, an evolutionary virologist at the Robert Koch Institute, says this marks the first time countries have taken such drastic actions as the U.K. lockdown and the travel bans based on genomic surveillance in combination with epidemiological data. Its pretty unprecedented at this scale, he says. But the question of how to react to disconcerting mutations in pathogens will crop up more often as genomic surveillance expands, he predicts. People are happy they prepared for a category 4 hurricane even if predictions turn out to be wrong and the storm is less severe, Calvignac-Spencer says. This is a bit the same, except that we have much less experience with genomic surveillance than we have with the weather forecast.

Although the rise of B.1.1.7 in the United Kingdom is troubling, Farrar says he is equally concerned about the other variant spreading quickly in South Africa and that has now been detected in two travelers in the United Kingdom as well. It includes two further mutations in the part of the spike protein that binds to its receptor on human cells, K417N and E484K. These could impact the binding of the virus to human cells and also its recognition by the immune system, Farrar says. These South African mutations I think are more worrying than the constellation of the British variant. South African hospitals are already struggling, he adds. Weve always asked, Why has sub-Saharan Africa escaped the pandemic to date? Answers have focused on the relative youth of the population and the climate. Maybe if you just increase transmission a bit, that is enough to get over these factors, Farrar says.

To Van Kerkhove, the arrival of B.1.1.7 shows how important it is to follow viral evolution closely. The United Kingdom has one of the most elaborate monitoring systems in the world, she says. My worry is: How much of this is happening globally, where we dont have sequencing capacity? Other countries should beef up their efforts, she says. And all countries should do what they can to minimize transmission of SARS-CoV-2 in the months ahead, Van Kerkhove says. The more of this virus circulates, the more opportunity it will have to change, she says. Were playing a very dangerous game here.

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U.K. variant puts spotlight on immunocompromised patients' role in the COVID-19 pandemic - Science Magazine


Study Finds Immune Issues in COVID-19 Patients With Acute Respiratory Failure – Times of San Diego

Saturday, December 26th, 2020

Share This Article:A nurse treats a coronavirus patient in an ICU. Image from Scripps video

Patients with severe COVID-19 disease who develop respiratory failure have malfunctions in their immune systems that distinguish them from other such patients, according to a new study.

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The findings could help doctors develop new ways to prevent and treat this life-threatening complication researchers said.

The Cedars-Sinai study, published Dec. 16 in the journal Cell Reports, focused on acute respiratory distress syndrome known as ARDS. The sudden-onset respiratory failure can occur when the lungs lining is damaged by illness or injury.

ARDS causes fluid to accumulate in the lungs and also causes air sacs in the lungs to collapse, impeding breathing and lowering the oxygen level in the blood.

Although most COVID-19 patients have mild respiratory illness, about 20% become seriously ill and require hospitalization due to pneumonia. That can progress to ARDS and systemic inflammation, according to recent research.

ARDS is associated with poorer outcomes, including death or lasting lung damage.

Because ARDS has such serious consequences for coronavirus patients, it is critical that we understand why it happens and what we can do to treat it, said Peter Chen, MD, professor of Medicine and director of the Division of Pulmonary and Critical Care Medicine at Cedars-Sinai. That is why we did this research.

The research team analyzed the immune systems of 17 COVID-19 patients five with moderate coronavirus disease, six with ARDS and six who were recovering from ARDS and compared these patients against three people without COVID-19.

They looked at the transcription process, which is how genes transfer their instructions to proteins that construct a cells chemical processes, in so-called peripheral blood mononuclear cells.

This category includes various types of highly specialized immune cells that fight infections.

The investigators uncovered a range of distinctive defects in the transcription processes of peripheral blood mononuclear cells in the ARDS patients, as compared with the other subjects in the study.

These defects appeared in cells in both of the bodys immune systems: the innate immune system, which initially responds to viruses and bacteria; and the adaptive immune system, which kicks in later.

The defects also affected how the body switched between innate and adaptive immunity.

Our study supports the concept that COVID-19, and especially severe cases that have progressed to ARDS, is characterized by multifaceted impairment of the bodys regulation of immune responses, said Helen Goodridge, Ph.D, associate professor of Biomedical Sciences and Medicine at Cedars-Sinai.

Future research using larger sample sizes is needed to further delineate the transcriptional landscape of immune cells in different ARDS populations, according to the study team.

In the meantime, Goodridge said, the implications of the findings are clinically relevant. They indicate that treatment of patients with ARDS arising from COVID-19 infections may require a targeted approach instead of broad, immunosuppressive therapy.

City News Service

Study Finds Immune Issues in COVID-19 Patients With Acute Respiratory Failure was last modified: December 25th, 2020 by Editor

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Study Finds Immune Issues in COVID-19 Patients With Acute Respiratory Failure - Times of San Diego


New Class of Dual-Acting Antibiotics Active Against a Wide Range of Bacteria – SciTechDaily

Saturday, December 26th, 2020

Bacteria image. Credit: The Wistar Institute

Dual-acting immuno-antibiotics block an essential pathway in bacteria and activate the adaptive immune response.

Wistar Institute scientists have discovered a new class of compounds that uniquely combine direct antibiotic killing of pan drug-resistant bacterial pathogens with a simultaneous rapid immune response for combatting antimicrobial resistance (AMR). These findings were published on December 23, 2020, in Nature.

The World Health Organization (WHO) has declared AMR as one of the top 10 global public health threats against humanity. It is estimated that by 2050, antibiotic-resistant infections could claim 10 million lives each year and impose a cumulative $100 trillion burden on the global economy. The list of bacteria that are becoming resistant to treatment with all available antibiotic options is growing and few new drugs are in the pipeline, creating a pressing need for new classes of antibiotics to prevent public health crises.

We took a creative, double-pronged strategy to develop new molecules that can kill difficult-to-treat infections while enhancing the natural host immune response, said Farokh Dotiwala, M.B.B.S., Ph.D., assistant professor in the Vaccine & Immunotherapy Center and lead author of the effort to identify a new generation of antimicrobials named dual-acting immuno-antibiotics (DAIAs).

Existing antibiotics target essential bacterial functions, including nucleic acid and protein synthesis, building of the cell membrane, and metabolic pathways. However, bacteria can acquire drug resistance by mutating the bacterial target the antibiotic is directed against, inactivating the drugs or pumping them out.

We reasoned that harnessing the immune system to simultaneously attack bacteria on two different fronts makes it hard for them to develop resistance, said Dotiwala.

Fluorescence microscopy staining showing the effects of DAIA treatment on bacteria viability. Credit: The Wistar Institute

He and colleagues focused on a metabolic pathway that is essential for most bacteria but absent in humans, making it an ideal target for antibiotic development. This pathway, called methyl-D-erythritol phosphate (MEP) or non-mevalonate pathway, is responsible for biosynthesis of isoprenoids molecules required for cell survival in most pathogenic bacteria. The lab targeted the IspH enzyme, an essential enzyme in isoprenoid biosynthesis, as a way to block this pathway and kill the microbes. Given the broad presence of IspH in the bacterial world, this approach may target a wide range of bacteria.

Researchers used computer modeling to screen several million commercially available compounds for their ability to bind with the enzyme, and selected the most potent ones that inhibited IspH function as starting points for drug discovery.

Since previously available IspH inhibitors could not penetrate the bacterial cell wall, Dotiwala collaborated with Wistars medicinal chemist Joseph Salvino, Ph.D., professor in The Wistar Institute Cancer Center and a co-senior author on the study, to identify and synthesize novel IspH inhibitor molecules that were able to get inside the bacteria.

The team demonstrated that the IspH inhibitors stimulated the immune system with more potent bacterial killing activity and specificity than current best-in-class antibiotics when tested in vitro on clinical isolates of antibiotic-resistant bacteria, including a wide range of pathogenic gram negative and gram positive bacteria. In preclinical models of gram negative bacterial infection, the bactericidal effects of the IspH inhibitors outperformed traditional pan antibiotics. All compounds tested were shown to be nontoxic to human cells.

Immune activation represents the second line of attack of the DAIA strategy, said Kumar Singh, Ph.D., Dotiwala lab postdoctoral fellow and first author of the study.

We believe this innovative DAIA strategy may represent a potential landmark in the worlds fight against AMR, creating a synergy between the direct killing ability of antibiotics and the natural power of the immune system, echoed Dotiwala.

Reference:IspH inhibitors kill Gram-negative bacteria and mobilize immune clearance by Kumar Sachin Singh, Rishabh Sharma, Poli Adi Narayana Reddy, Prashanthi Vonteddu, Madeline Good, Anjana Sundarrajan, Hyeree Choi, Kar Muthumani, Andrew Kossenkov, Aaron R. Goldman, Hsin-Yao Tang, Maxim Totrov, Joel Cassel, Maureen E. Murphy, Rajasekharan Somasundaram, Meenhard Herlyn, Joseph M. Salvino and Farokh Dotiwala, 23 December 2020, Nature.DOI: 10.1038/s41586-020-03074-x

Publication information: IspH inhibitors kill Gram-negative bacteria and mobilize immune clearance, Nature (2020). Online publication.

Co-authors: Rishabh Sharma, Poli Adi Narayana Reddy, Prashanthi Vonteddu, Madeline Good, Anjana Sundarrajan, Hyeree Choi, Kar Muthumani, Andrew Kossenkov, Aaron R. Goldman, Hsin-Yao Tang, Joel Cassel, Maureen E. Murphy, Rajasekharan Somasundaram, and Meenhard Herlyn from Wistar; and Maxim Totrov from Molsoft LLC.

Work supported by: The G. Harold and Leila Y. Mathers Foundation, funds from the Commonwealth Universal Research Enhancement (CURE) Program and the Wistar Science Discovery Fund; The Pew Charitable Trusts supported Farokh Dotiwala with a Wistar Institute recruitment grant; Additional support was provided by the Adelson Medical Research Foundation and the Department of Defense. Support for The Wistar Institute facilities was provided by Cancer Center Support Grant P30 CA010815 and National Institutes of Health instrument grant S10 OD023586.

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible.

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New Class of Dual-Acting Antibiotics Active Against a Wide Range of Bacteria - SciTechDaily


Can a smile reduce the pain of an injection? – Medical News Today

Saturday, December 26th, 2020

A recent study finds that both smiling and grimacing could reduce the sensation of pain associated with a vaccination-like needle injection. A sincere smile also reduced stress-induced physiological responses in participants.

When humans face acute pain, they tend to close their eyes tightly, raise their cheeks, and bare their teeth. Certain animals use similar facial expressions, which experts often call the grimace response.

As the authors of the recent study explain, these facial musculature changes can also have a different interpretation: smiling.

Why these two expressions, which occur for very different reasons, should share so many aspects is unclear. Researchers from the University of California, Irvine School of Ecology recently set out to test whether these facial movements are beneficial in the context of stress and pain.

Specifically, they wanted to understand whether manipulating participants facial expressions during a needle injection might impact their experience of pain and associated stress levels.

The researchers findings appear in the journal Emotion.

For many years, scientists have been interested to understand the impact of facial expressions on pain perception and mood. The facial feedback hypothesis, for instance, states that activating facial muscles can enhance or reduce emotional experiences. These effects on emotion can occur even if researchers manipulate a participants facial muscles into an expression.

As the authors of the recent study explain, feigning a smile, whether conscious or not, may alter emotions in a positive way.

To investigate possible links between facial expression and pain sensation, the researchers recruited 231 participants. The participants all received a shot of saline solution using a needle similar to those used to deliver a flu vaccine.

The researchers split the participants into four groups. Before and during the shot, the scientists manipulated participants faces into the following different expressions using chopsticks held in the mouth:

Example photographs of how the researchers used the chopsticks to elicit these expressions are available here.

Before the injection, participants completed a questionnaire that asked how anxious they were about the needle.

As the participants held their facial expressions, a medical practitioner administered the saline injection. Once the practitioner had applied a bandage, the participant removed the chopsticks from their mouth and completed a questionnaire about how much pain they were experiencing.

After 6 minutes of rest, the participants once again reported their pain levels. The researchers also asked them how stressful the experience was.

Before, during, and after the injection, the participants were linked to an electrocardiogram. Additionally, the researchers measured changes in the electrical resistance of participants skin, or electrodermal activity (EDA). EDA is a measure of psychological or physiological arousal.

According to the authors, the effect of the induced facial expression was strongest immediately after the injection. They explain that the Duchenne smile and grimace groups reported approximately 40% less needle pain versus the neutral group.

When the researchers examined heart rate data, they found that the Duchenne smile group had significantly lower heart rates than the neutral group. There were no significant differences between the other groups.

As for EDA, they only noted marginal benefits in the Duchenne smile group. Overall, the authors conclude:

Together, these findings indicate that both smiling and grimacing can improve subjective needle pain experiences, but Duchenne smiling may be better suited for blunting the stress-induced physiological responses of the body versus other facial expressions.

The study does have some limitations. Firstly, there were only 66 participants in the Duchenne smile group, the largest of the four experimental groups.

Also, 83.5% of the participants were white, meaning that the results might not apply to other groups. As the authors note, the participants were also relatively young and healthy.

It is also worth noting that holding chopsticks in a persons mouth is relatively unnatural and does not truly replicate a natural facial expression. And, as the authors write, expression in this study did not meet the intensity of true emotional experience.

However, principal investigator, Prof. Sarah Pressman, is upbeat about the findings:

Our study demonstrates a simple, free, and clinically meaningful method of making the needle injection less awful. Given the numerous anxiety- and pain-provoking situations found in medical practice, we hope that an understanding of how and when smiling and grimacing helps will foster effective pain reduction strategies that result in better patient experiences.

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Can a smile reduce the pain of an injection? - Medical News Today


Drink This "Fire Cider" Elixir to Boost Immunity and Stay Heathy – The Beet

Saturday, December 26th, 2020

First of all let's get one thing clear: Nothing you eat or drink can keep you from getting the COVID-19 virus, but there are things you can drink or eat to stay healthy, boost your immune system, and try to lower your chances of having severe symptoms if you do contract it or any virus or cold for that matter this winter.

Here's your best bet on how to make an at-home tonic that will strengthen your immune system and protect your body from suffering the most severe symptoms if you do happen to catch something.

Like any virus, such as the flu or a cold, taking care of yourself is the best way to give your body the strength it needs to fight the invaders. In the case of COVID-19, wear a mask, wash your hands, and if you get it, quarantine, rest anddrink plenty of fluids.

The term "fire cider" has been popular since the late 70s or early 80s, created by an herbalist and recently the subject of a bigger court case about whether a company could trademark the name, which previously referred broadly to an at-home natural remedy tonic full of onions, garlic, spices, vinegar and more (The herbalists lost, leading fans of natural remedies feeling that this was a miscarriage of justice because to them it would be like branding the words ice tea).

The case was covered widely, since home remedies have been around for eons, and are often used when modern medicine comes up short, leaving every individual to fend for themselves. This is the case with new diseases such as the coronavirus since while we wait for the vaccine to become widely available, people are turning to health tonics, elixirs, and teas to try to boost their immunity.

"Yes, this type of elixir has been around for a long time. In herbal medicine, we call it an oxymel," explains Dr. Chad Larson, NMD, DC, CCN, CSCS, advisor and consultant for Cyrex Laboratories. "With the dominanceof the pharmaceuticalindustry, many of these very therapeutic remedies are becoming a lost art. Hippocrateswrote about using oxymels over two thousand years ago, to help release sputum and soothe the upper respiratory tract."

Dr. Larson sharedaninterestingblog post on oxymels, from Mountain Rose Herbs, which clarifies that not all elixirs are oxymels since the term refers to one that mixes acidic ingredients like apple cider vinegar with honey. Meanwhile,the term "fire cider"was made popular by anherbalist Rosemary Gladstar, and her fellow plant-medicine colleagues, and they recently tried without success to fight the trademarking of the name "fire cider" by a company that sells a version of it in bottled form. The casewas well watched by those interested inthe right to keep traditional remedies free of trademark restrictions, to no avail, the blog reports.

'Oxymel' describes a combination of known immune-boosting ingredients mixed into hot water that when ingested daily can add powerful antioxidants, vitamin C, zinc, and other compounds that are known to arm your cellular defenses against viral invaders. Since long before modern medicine, healers have used ginger, turmeric, horseradish, garlic, and lemon to treat ailments from congestion to indigestion. These may not kill the dreaded coronavirus, but if you are taking every other preventative measure, (mask-wearing, hand-washing, social -isolating) what could be the harm?

We have done stories at The Beet on the anti-inflammatory properties of ginger and the vitamin C benefits of lemon in hot water (which many people drink in the morning to aid digestion rather than coffee to start the day) and the immunity-boosting compounds in garlic and the anti-inflammatory properties abs multi-benefits of turmeric. So it makes sense that combining these roots and fruits into an elixiralongsidethe benefits of apple cider vinegar and spices can supercharge your immune system.

What to drink to boost immunity and the benefits of creating your own hot tea or elixirs with a combination of:

A Note about honey: If you want toadd honey to sweeten it, but if someone is vegan they choose not to eat honey since it is an animal bi-product.

Most recipes call for you to chop up all of thefruits, vegetables, and roots, add to an airtight glass jar, cover with your herbs and then fill with apple cider vinegar an inch or two past the herbs, and let sit in a warm place for a couple of weeks, shaking the jar daily. After a few weeks, strain out the liquid, and add a sweetener like honey (or agave if you're vegan) and it's ready to drink.

There are many different ways to ingest this folk remedy: You can takea couple of tablespoons in the morning like an immunity shot, add it to tea or hot water to dilute the strong taste, or incorporate it into your recipes as a marinade or salad dressing. You can even soak a cloth in your tonic and rub it on your chest to ease congestion.

Toomuch to keep on hand? Assuming you have all these ingredients or are pressed for time or don't want tocreate your own tonic, to buy it premade, try this Fire Ciderto drink instantly.

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Drink This "Fire Cider" Elixir to Boost Immunity and Stay Heathy - The Beet


Sex hormones, chromosomes might play a role in better Covid outcomes in women than men, says study – Economic Times

Saturday, December 26th, 2020

TORONTO: Women face less severe complications and a lower risk of dying from COVID-19 than men due to the presence of hormones and chromosomes that contribute to a stronger immune response in female patients, according to a study.

The research, published in the American Journal of Physiology-Heart and Circulatory Physiology, highlights how the sex differences in COVID-19 are linked to ACE2, an enzyme that acts as the receptor allowing SARS-CoV-2 virus to enter the body.

ACE2 is also key in protecting against cardiovascular, lung and kidney diseases, the researchers said.

"Because of their chromosomes, women have two copies of the ACE2 gene and men have only one copy," said senior study author Gavin Oudit, professor at the University of Alberta in Canada.

"This does not seem to make women more susceptible to COVID-19 infection, but it does protect them from the complications associated with the virus," Oudit said.

ACE2 is an X chromosome-linked gene, Oudit explained.

This means women have twice as many active genetic instructions to make ACE2, he said. Another gene that is twice as strong in women due to this X-inactivation escape is called Toll-like receptor seven, a key part of the innate immune system.

"The stronger presence of Toll-like receptor seven in women explains why women's immune systems are stronger than men's and can tolerate virus infection better, including the common cold," said Oudit, adding "the man-cold phenomenon is real."

The study found that men face more severe illness and poorer outcomes around the world, even when women likely face more exposure to SARS-CoV-2 than men.

"Due to gender issues, women face more risk, so it's reassuring to know that their outcomes are not any worse; in fact they are clearly better than men's," Oudit said.

The researchers said they are trying to understand how manipulating ACE2 levels might help COVID-19 patients, to prevent infection by blocking the enzyme or to protect the cardiovascular system, lungs and kidneys by enhancing it.

"We need to look at the factors that are responsible for better outcomes for everyone, taking sex differences into consideration when we test new therapies and provide COVID-19 care," Oudit said.

Whether the pandemic ends within a month or two or stretches into the long-term, business owners need to be ready to adapt and make changes to their business strategy in order to weather the storm and beyond. Here are a few tips to start implementing and planning form the CEOs.

- Absorb and accept technology in your organization to take your product to the customers

- Take initiative and bring smarter consumer propositions to take care of worries of a consumer while buying property

- Reskill your teams for the new scenarios

- Mitigate risk and judicious cash management. Most importantly stay positive during this time.

- There needs to be a diligent revision of sales, revenue goals and product timelines along with a new operating plan in place. Companies should strategize and communicate transparently with the stakeholders and customers to understand their perception of the products/services being offered.

- Also, to avoid bitterness with the contracted parties, companies should give sufficient notice to the vendors, suppliers and landlords in case of any delay in the payments.

- When it comes to the capital, companies should stay patient with fundraising. Considering the criticality of the situation, investors may take longer than usual to make funding decisions after following stringent diligence procedures.

Contingency Planning: Planning always saves you from the worst case scenarios. Always have Plan B and if possible Plan C also so that if something goes sideways, your company will not be hit hard as it will be saved by your contingency plans.

Quick Decision Making: Never delay in making decisive decisions in times of trouble. And never be shy about seeking help from outside.

Communicate with Customers: Try to communicate with customers and let them know that they and their reviews on your products matter. Improve and do the changes accordingly, if needed.

Internet: Go online as much as possible because it always helps to reach customers who we cannot tap through offline or other forms of marketing.

Keep Striving: Keep striving to come on top of the industry of which your company is a part of.

Marketing approach: This is an excellent time to relook at the channel marketing approach. Maximizing free channels like SEO and owned media like website and social media to communicate and engage with the customers. And build further marketing efficiency while starting the channels that require spend

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Sex hormones, chromosomes might play a role in better Covid outcomes in women than men, says study - Economic Times


The first Covid vaccines were triumphs. What if the next are only OK? – POLITICO

Saturday, December 26th, 2020

The Trump administration doubled its orders from Pfizer and Moderna this month to 200 million doses each. But both vaccines are given as two doses per person, meaning the U.S. supply will only cover 200 million of the nation's 250 million adults. Authorizing more vaccines for emergency use could immediately increase that stockpile, and also help ensure sufficient vaccine when inoculation is allowed for teens and children.

Johnson & Johnson is preparing to release the first efficacy data on its shot, which is given as a single dose, in January. AstraZeneca could also release more data as early as next month from its late-stage trials, officials with the federal government's Operation Warp Speed said recently. (The company said in a statement that it has "no further updates on the US specific trial.")

An early frontrunner in the global vaccine race, AstraZeneca has sold more shots worldwide than any other manufacturer. Between agreements with the World Health Organization, the Coalition for Epidemic Preparedness and Innovation and the Serum Institute, a mass manufacturer in India, the British drugmaker has promised nearly 1 billion shots to other countries not including the 300 million it pledged to the U.S.

AstraZenecas vaccine is vastly cheaper than others and much easier to ship and store than vaccines such as Pfizers, that require ultra-cold freezers or dry ice. That makes it an appealing option for hard-to-reach areas in the U.S., as well as lower-income countries with less advanced infrastructure.

But the outlook for the company's vaccine is hazy after AstraZeneca reported last month that nearly 3,000 trial volunteers in the U.K. were accidentally given a half-strength first dose. The regimen proved 90 percent effective in early data, beating the 62 percent efficacy of two standard doses. Some vaccine experts think the lower dose's success could be a statistical fluke, since 3,000 people is a small slice of the tens of thousands of people enrolled in the company's trials; others say it could indicate a clearly better option.

AstraZeneca would still have to fully test the lower dosing regimen before applying to the Food and Drug Administration for emergency-use authorization. The agency is also requiring that drug companies follow at least half the trial volunteers for two months after their last dose.

A company spokesperson said that there is "nothing to share on U.S. filing plans at this time."

But the FDA's minimum criteria for seeking authorization do not tell the full story of a vaccine's value, said Peter Hotez, a virologist and dean of the National School of Tropical Medicine at the Baylor College of Medicine.

Initial efficacy over the first two months is only one of several aspects that requires consideration," said Hotez, who is also developing a potential coronavirus shot with partners in India. Other vaccines may offer advantages in terms of durability of protection, tolerability, safety, suitability for children or adolescents, and for that well require additional vaccines.

Pfizer and Moderna only recently started studying their vaccines in children as young as 12 years old, and no manufacturer has begun trials in children even younger. Regulators have also called for more data in pregnant women and for certain risk factors like heart disease, diabetes and other illnesses that could affect the immune system. Health experts say that a vaccine that may only work moderately overall may be best for key subpopulations, such as pregnant women.

The latest news in health care politics and policy.

And some of the vaccines still in development may prove easier to manufacture, transport or administer than the Pfizer and Moderna shots.

Both of those authorized vaccines use relatively new messenger RNA technology to instruct cells to make a protein found on the virus, which revs up the body's immune system. J&J and AstraZeneca use a more traditional method, in which small bits of DNA from the coronavirus are edited into a weakened version of another virus called an an adenovirus. When the adenovirus enters cells, they read its DNA and produce a protein found in the coronavirus.

One theory about the AstraZeneca dosing confusion is that a full dose of the adenovirus triggered too big of an immune response so the body didnt have time to learn much about the coronavirus it was meant to protect against, said Rasmussen. There is still value in having that information, because maybe [AstraZeneca] can start assessing that half-dose regimen.

But the AstraZeneca data could present a quandary for FDAs independent vaccine advisory panel, which has been meeting publicly to discuss each candidate in a bid to boost transparency and public confidence. The company has said that combined results so far from its Phase III trials show its vaccine to be 70 percent effective. But the two dosing regimens tell different stories: 90 percent is basically comparable with the existing vaccines; 62 percent is not.

You cant reasonably combine data from two different dosing strategies, two different dosing intervals and two different placebo groups, Paul Offit, a vaccine expert at the University of Pennsylvania who sits on the FDAs expert panel, the Vaccines and Related Biological Products Advisory Committee.

It also presents a sticky situation for the largest national vaccination plan in history. While the two vaccines authorized now have nearly identical efficacy and safety profiles and use the same technology, having a more varied roster of vaccines would be harder to distribute fairly.

There are obvious ethical issues: If one vaccine is more effective than the others, who gets what, right? said Philip Landrigan, director of the global public health program at Boston College, who stressed the importance of clear federal planning if that happens. Transparency and openness have another benefit beyond just ensuring that the system works well it could persuade people who are reluctant to get the vaccine.

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The first Covid vaccines were triumphs. What if the next are only OK? - POLITICO


New research highlights the importance of the thymus in successful pregnancies – University of Birmingham

Saturday, December 26th, 2020

Researchers found that during pregnancy, the female sex hormones instruct the thymus to produce Tregs specialised in dealing with physiological changes during pregnancy.

How the immune system adapts to pregnancies has puzzled scientists for decades. Now, findings from an international group of researchers, led by experts at Karolinska Institutet in Sweden, reveal important changes that occur in the thymus to prevent miscarriages and gestational diabetes. The study was published today (23 December 2020) in Nature.

The thymus is a central organ of the immune system where specialised immune cells called T lymphocytes mature. These cells, commonly referred to as T cells, then migrate into the blood stream and tissues to help combat pathogens and cancer. An important T cell subset, known as a regulatory T cell or Treg, is also produced in the thymus. The main function of a Treg is to help regulate other immune cells.

Researchers found that during pregnancy, the female sex hormones instruct the thymus to produce Tregs specialised in dealing with physiological changes during pregnancy. The studywhich involved researchers at Karolinska Institutet, the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) in Vienna, University of British Columbia in Vancouver, further reveals that RANK, a receptor expressed in the thymus epithelia, is the key molecule behind this mechanism.

The study builds on work by a team at the University of Birmingham as researcher and collaboratorProfessor Graham Andersonfrom the Institute of Immunology and Immunotherapy explains: In 2007, our lab provided the first evidence that RANK plays a critical role in controlling thymus function in the steady state immune system. Now, this new research shows how RANK in the thymus regulates the immune system in pregnancy, which is an exciting new direction.

We knew RANK was expressed in the thymus, but its role in pregnancy was unknown, says first and co-corresponding author Dr. Magdalena Paolino, assistant professor at the Department of Medicine, Solna, Karolinska Institutet.

To get a better understanding, the authors studied mice where RANK had been deleted from the thymus.

The absence of RANK prevented the production of Tregs in the thymus during pregnancy. This resulted in less Tregs in the placentas, leading to miscarriages, continues Magdalena Paolino.

This latest study further shows that in normal pregnancies, the produced Tregs also migrate to the mothers fat tissue to prevent inflammation and help control glucose levels in the body. Pregnant mice lacking RANK had high levels of glucose and insulin in their blood and many other indicators of gestational diabetes, including fetal macrosomia.

Similar to babies of women with gestational diabetes, the newborn pups were much heavier than average, explains Magdalena Paolino.

In addition, the deficiency of Tregs during pregnancy was proven to result in long-lasting transgenerational effects on the offspring, which remained prone to diabetes and overweight throughout their life spans. Giving the RANK deficient mice thymus-derived Tregs that had been isolated from normal pregnancies, reversed all issues including fetal loss and maternal glucose levels and the body weights of the pups.

The researchers also analysed women with gestational diabetes, revealing a reduced number of Tregs in their placentas, much similar to the study on mice.

This research changes our view of the thymus, as an active and dynamic organ required to safeguard pregnancies, Magdalena Paolino says. It also provides new molecular insight for gestational diabetes, a disease that affects many women and which we still know little about. It emphasises the importance of clinics detecting and managing glucose metabolism in pregnant women to avert its long-term effects.

Co-corresponding author Dr. Josef Penninger notes that how rewiring of the thymus contributes to a healthy pregnancy was one of the remaining mysteries of immunology until now.

Our work over many years has now not only solved this puzzle pregnancy hormones rewire the thymus via RANK but uncovered a new paradigmatic function: the thymus not only changes the immune system of the mother to allow the fetus, but it also controls metabolic health of the mother, Josef Penninger says.

The study was possible thanks to a close collaboration between the laboratory of Magdalena Paolino at Karolinska Institutet and the laboratories of Josef Penninger at IMBA and UBC. Researchers from the CeMM Institute and the Medical University of Vienna, as well as from the Universities of Birmingham and Oxford also participated.

For more information please contactMagdalena Paolino, Assistant Professor,Department of Medicine Solna, Karolinska Institutet.

Full paper:RANK links thymic Tregs to fetal loss and gestational diabetes in pregnancy, Magdalena Paolino*, Rubina Koglgruber, Shane J. F. Cronin, Iris Uribesalgo, Esther Rauscher, Juergen Harreiter, Michael Schuster, Dagmar Bancher-Todesca, Blanka Pranjic, Maria Novatchkova, Andrea White, Verena Sigl, Sabine Dekan, Juan P. Fededa, Thomas Penz, Christoph Bock, Lukas Kenner, Georg A. Hollnder, Graham Anderson, Alexandra Kautzky-Willer, and Josef M. Penninger*, Nature, in press 23/12/2020


Grant information:

The researchers were supported by grants from Karolinska Institutet, the Ragnar Soderberg Foundation, the Swedish Research Council, the Swiss National Foundation, The Wellcome Trust, MRC, CRUK, Austrian Science Fund, European Training Network, IMBA, a Canada150 Chair, the T. von Zastrow foundation and the European Research Council.

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New research highlights the importance of the thymus in successful pregnancies - University of Birmingham


Drinking This One Thing Every Day May Help Weaken COVID-19 – Eat This, Not That

Saturday, December 26th, 2020

With a coronavirus vaccine right around the corner, it feels like we are almost out of the woods. Don't get ahead of yourselfaccording to the BBC, healthy Americans under the age of 65 won't start getting the vaccine at least until April, with the inoculation efforts stretching throughout 2021. We still have months ahead of us and still have plenty of time to contract COVID-19 if we let our guard down, which is why it's important to find ways to combat the viruslike this one drink to weaken COVID.

If you happen to contract a milder form of the illness, you have some light treatment options at your disposal. According to Johns Hopkins, drinking fluids and taking over the counter medicine to reduce the fever can help get you feeling better, but if you want an extra holistic boost that can help reduce the symptoms of COVID, look no further than a daily glass of pumpkin seed milk.

Here's why, and for more tips during COVID, here's The One Vitamin Doctors Are Urging Everyone to Take Right Now.

"Your immune system right now is very busy filtering your cells to know which are the safe ones and which do not belong to your body," says Jason Hughes, RD and head coach of Vegan Liftz. "Thus, it needs a daily dose of vitamins and minerals from the foods you eat and the beverages you drink, to keep you active."

"[One] drink to weaken the symptoms of viruses such as COVID-19, and to strengthen your immune system, is Pumpkin Seed Milk," Hughes continued. "This drink consists of fresh and natural ingredients, which makes it very healthy, and at the same time, delicious. Pumpkin seed milk boosts your immune system, making it a lot stronger to fight viruses and infections. Pumpkin seed is a great source of zinc, and other vitamins and minerals, which are the nutrients you need to prevent COVID-19."

According to Healthline, pumpkin seed milk has officially been studied in U.S. clinical trials exploring zinc's effect on reducing coronavirus symptomsand has been proven to reduce inflammation and improve one's immune system. Even if you don't have COVID-19 symptoms, the drink helps promote bone, urinary, and prostate health among several other factors, making it an exciting, healthy drink to keep an eye on.

If you test positive for COVID-19, follow the advice of the Harvard School of Health and self-isolate as soon as you can and avoid contact with other family members or roommates. If you begin having trouble breathing or feel like you run out of breath easily, visit the emergency room as soon as possible.

If you have mild symptoms, a glass of pumpkin seed milk might have you back on your feet sooner than expected. Even when you start feeling better, incorporating a glass of this hot, new beverage might be just the thing you need to stay healthy.

For more healthy tips, be sure to sign up for our newsletter.

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Drinking This One Thing Every Day May Help Weaken COVID-19 - Eat This, Not That


Covaxin found to be safe, effective in phase 2 trial – Mint

Saturday, December 26th, 2020

Bharat Biotechs indigenous vaccine Covaxin induced immunity against covid-19 through antibodies as well as T-cells and was found to be safe with no serious adverse events during its first two stages of trial, a pre-print of the phase 2 study showed.

It is hypothesised that the humoral and cell-mediated responses reported in this study may persist until at least 6-12 months after the second vaccination dose," showed the trial report, which is yet to be peer-reviewed.

Also Read | Inside the farmer disquiet at Delhis doorstep

Humoral immune responses are caused by antibodies, while cell-mediated responses are caused by T-cells, which are major components of the adaptive immune system whose roles include killing infected host cells, activating other immune cells, producing cytokines and regulating the immune response. They are the second level of the bodys immune system after antibodies that are meant to attach to the pathogen and stop it from infecting cells.

BBV152 induced binding (to both spike- and nucleocapsid protein epitopes) and neutralizing antibody responses that were similar to those induced by other SARS-CoV-2 inactivated vaccine candidates," the study showed, adding that a sizeable memory T-cell population was also observed three months after the second and final dose was given.

The vaccine was tested in 380 healthy children and adults as part of the phase 2 immunogencity study, with half of them getting a 3 microgram of antigen, along with adjuvant, and the rest getting twice that dose of antigen and the adjuvant.

The primary objective of the study was to determine seroconversionhow many of the participants showed antibodies in their immune systemwhile the secondary outcome was to determine the safety and side-effects.

Covaxin was shown to induce T-cell memory responses and showed the ability to make the body secrete spike-specific IgG antibodies. An inactivated vaccine is basically a dead coronavirus, with the company also using an adjuvant to boost the immune response.

A pre-print of the company safety data in phase 1 trials was also released last week. It showed that one of the nearly 300 participants who were part of the vaccine arms of the Covaxin phase 1 trial showed serious side-effect during the trial. The side-effect was deemed as not related to the vaccine, showing that the shots were safe to use.

The company said that the study had several strengths, including the fact that it enrolled participants with a wide range of ages and found no differences in immune responses across age groups.

Davinder Gill, a vaccine expert in the US, said in the phase 2 trial, Bharat Biotech seemed to want to fix the dose for its phase 3 trial and later, and found that the 6 microgram dose with the adjuvant was more effective at inducing the production of neutralizing antibodies.

Compared to the data that I have seen in other phase 2 studies from AstraZeneca, Pfizer and Moderna, Bharat Biotech for sure put out a lot more data. They have looked at various ways of measuring antibodies and various ways to look at neutralizing antibodies. But on the flipside, instead of more data, I would have liked to see a phase 2 maybe in 1,000-1,200 subjects, particularly because they were expanding the age group from 18-55 to 12-65 years," Gill said.

Bharat Biotech is currently conducting a phase 3 study of 26,000 participants to determine the efficacy of the vaccine.

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Covaxin found to be safe, effective in phase 2 trial - Mint


New Year’s Resolution is the Perfect Time to Add Health Addiction’s Functional Supplements to Your Health Regimen – GlobeNewswire

Saturday, December 26th, 2020

PALM BEACH, FL, Dec. 23, 2020 (GLOBE NEWSWIRE) -- Getting healthy is a popular resolution for the New Year, which is just days away.

The New Year is a perfect time for everyone to think about their health, said Marcus, founder and functional nutritionist for Health Addiction, a wellness company in Mexico City.The COVID-19 pandemic has forced people to think about their health.

During the past nine months, Ms. Marcus said Americans have searched for any health advantage that would boost their immune system and keep them healthy.

For the New Year, I want people to continue to prioritize their health. Make health your number one priority, Ms. Marcus said, adding that people should take a holistic approach to their health.

You should start eating healthy foods. Begin an exercise routine, she added.

Ms. Marcus, who knows that more than 70 percent of American consumers take dietary supplements for their health, plans to introduce eight popular functional supplements to the U.S. market this year.

Our Health Addiction supplements provide a holistic approach to keep people healthy, Ms. Marcus said. We have supplements that target the gut, immune system, cardiovascular health, and joints."

Health Addictionsfunctional supplements that will be available in the U.S. are:

We know people want to get and stay healthy, Ms. Marcus said. The New Year is the perfect time to begin a new health regimen. We branded our supplements, Health Addiction, because we want people to get addicted to good health. Now is an excellent time to start.

For more information, please visit Health Addiction online.

New Year's Resolution is the Perfect Time to Add Health Addiction's Functional Supplements to Your Health Regimen - GlobeNewswire


Aftereffects of COVID-19 can cloud the brain, or even cause strokes – CT Insider

Saturday, December 26th, 2020

NEW HAVEN As the COVID-19 pandemic enters its second year, neurologists are finding that patients frequently suffer difficulties in concentration and memory, even after recovering from the acute illness.

In some cases, chemicals formed to fight the coronavirus are causing bleeding in the brain and even strokes, though the instances of these are rare.

Dr. Serena Spudich, a neurologist with the Yale School of Medicine, is one of a team operating a neuro-COVID clinic, which has been see patients via telehealth visits. The clinic began seeing patients monthly, but now is run four times a month. There have been about 30 patients seen so far, Spudich said.

As the pandemic has progressed, we started to realize that there seemed to be some impact in the nervous system and that was something that other clinicians, other investigators in Asia and Italy and the United Kingdom were seeing, Spudich said.

The neurological issues patients were having after the major COVID symptoms had gone were so frequent that a specialized clinic was created within the Yale Medicine practice, including Dr. Shelli Farhadian and Dr. Lindsay McAlpine.

We wanted to get prepared because we realized there would be a variety of conditions that patients would be coming in with, Spudich said.

Headache has been one of the most common complaints, some of them persistent or severe enough to interfere with daily living, Spudich said. Other issues contribute to brain fog.

The primary concern is the sense that they are having trouble with concentration, memory and daily functioning in their lives, Spudich said.

Patients reported that they could not focus on their work or studies or had difficulty falling asleep or waking up.

Many of these issues are fairly subtle for the patients, so they may be able to function on a daily basis, she said. But the range of neurological symptoms has been broad, including a burning sensation on the skin, weakness and visual changes.

Its not the majority that theyre so debilitated that they cant work, Spudich said. Perhaps a fifth suffer that severely.

For most, its really remarkable what people continue to work through, she said.

Besides physical symptoms, theres also a significant mental health issue that some patients are exhibiting, including depression, anxiety and post-traumatic stress disorder, Spudich said. Theres always been a link thats been presumed between brain inflammation and some mental health and mood disorders.

Dr. Arman Fesharaki-Zadeh, a behavioral neurologist and neuropsychiatrist, is part of the clinics team.

Its not necessarily the coronavirus that causes neurological problems. Often its the bodys attempt to fight off the infection, the doctors noted.

One major issue with COVID is it causes a lot of inflammation in the body, Spudich said. That triggers the bodys immune system, which releases cytokines, proteins such as interferon and interleukin.

While not necessarily a cytokine storm that overwhelms the body, the response still can cause problems when the chemicals pass through inflamed blood vessels into the brain.

It doesnt seem that the virus, SARS-CoV-2, which causes COVID, is robustly affecting the brain, which is good, but even though maybe the virus itself isnt attacking the brain the immune response seems to be causing these problems, Spudich said.

Many of these patients were seeing were never severely ill. They were never severely ill in the ICU, Spudich said, but the cytokines released by immune cells are enough to cause lingering aftereffects.

It may be that addressing immune issues would address all the underlying issues that were seeing, she said. Theres so much we dont know. This is all the best hazard of a guess. What were doing basically is trying to listen to each patients story, how sick were they, what kind of lab values did they have, how long were they sick, what they were treated with.

In some cases, COVID may have exacerbated neurological problems the patient had before; in other cases they could be new symptoms.

While the neuro-COVID clinic treats patients, Dr. Amit Mahajan, assistant professor of radiology and biomedical imaging at Yale School of Medicine, has been researching the effects of the disease on the brain, using CT scans and MRIs. He is corresponding author of a study in the American Journal of Radiology of patients in the New York metropolitan area at the beginning of the pandemic.

What Mahajan and his co-authors found was a number of brain bleeds and clots forming in the brains of COVID patients. The numbers are small. In another study, 8.4 percent of admitted patients had such severe symptoms, he said. The number would be lower if all COVID patients were scanned.

Most of the problems, the real serious problems that happen with COVID, are due to something called inflammation in the blood, Mahajan said. And a lot of the people have developed clots because of the inflammation If they go and occlude the vessels of the brain, they may cause a stroke as well.

Problems also develop when the bodys clotting and anti-clotting processes are out of balance. Then you can not only have clots, you can also have bleeding, Mahajan said. The problem can be made worse if a patient is given blood-thinning medication, he said.

Another issue is what Mahajan called post-infectious phenomena, in which an immune response to the infection can cause its own problems. And that would include things like Guillain-Barre syndrome, in which the immune system attacks the nerves, as well as multisystem inflammatory syndrome in children.

For more information about the neuro-COVID clinic, call 203-785-4085.

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Aftereffects of COVID-19 can cloud the brain, or even cause strokes - CT Insider


What If You Could Change Your Immune System By Wearing Earbuds? Meet The Startup That Could Make It Possible – Forbes

Monday, December 14th, 2020

Non-invasive, wearable tech could usher in a new generation of personalized therapeutics. Unveiled ... [+] today, startup Nsos aims to treat rheumatoid arthritis by reinforcing the brains natural pathways.

They look like earbuds, feel like earbudsbut when you put them in, theyre completely silent. Thats because these earbuds arent for playing music or listening in on a video call. Instead, they deliver a finely-tuned electrical field to the brain.

Unveiled today, the earbud-like devices are a revolutionary rheumatoid arthritis treatment pioneered by neurotech startup Nsos.These wearable therapeutics may sound like science fiction. Even Nsos founder and CEO, Konstantinos Alataris, calls them a moonshot idea. But according to the data from Nsoss first clinical study, these devices are hardly far-fetched.

Normally, autoimmune diseases are treated with medication. In the case of rheumatoid arthritis, the current best treatments are over-the-counter pills like ibuprofen or prescription immunosuppressants like Humira. But these medications are not without side effects. And in the case of Humira, the medication must be injected under the skin, an uncomfortable routine for many patients. But what if there was a way to treat painful conditions like rheumatoid arthritis without pills or needles?

What if the medicine was electric?

Thats what Nsos is aiming to achieve through a novel therapeutic approach the company is dubbing e-mmunotherapy. If successful, this will be the first wearable, non-invasive treatment for an immune system disorder.

Neuroscience and immunology were once thought to be completely separate fields. But its now understood that these two systems are in constant communication with each other. The brain simultaneously generates thoughts and actions while taking care of critical functions like heartbeat and body temperature. It turns out that the brain also plays a major part in regulating inflammation. When these neural inflammation networks go haywire, it can result in immune system disorders like rheumatoid arthritis.

Nsos first e-mmunotherapy proof of concept works by sending electrical signals to the brain to reinforce its natural pathways. This is an opportunity to take a biological pathway, how the brain controls an overactive immune response, and restore it using an electrical field, mimicking the brain's language, says Alataris. So far, the companys wearable tech approach looks promising. Patients of the companys pilot clinical trial reported reduced severity of their rheumatoid arthritis symptoms comparable to the results of current medications.

Nsos Founder and CEO, Konstantinos Alataris, PhD.

Alataris already has deep experience in electrical therapeutics. He was previously the founder and CEO of Nevro, a company that produces subdural spinal cord stimulation devices for chronic pain. Similar startups, like Elon Musks Neuralink, rely on implanted electrode arrays. But this is the first time that electrical signals will be delivered through a fully external device.

If approved, these devices could dramatically simplify the treatment for inflammation-driven conditions. The earbuds would only need to be worn for a few minutes each day and the positive effects would increase over time. By reinforcing the proper neural pathways, the devices teach the brain to remember the positive changes. Not only does this provide sustained relief, it also hits closer to the root of the illness, addressing brain signals rather than chemical ones.

Nsos also recognizes the unique nature of each patients condition. Using machine learning, Alataris says the devices will eventually be able to deliver personalized electric fields depending on a patient's disease progression. Your therapy, your electrical field, your path sequence, at the end [they] will be different than mine, says Alataris.

With $16.5 million in funding led by Mayfield Fund, Nsos is already in process to test their devices in randomized control trials. If successful, the results will be submitted for FDA approval. But Alataris is clear that it will be years before these devices can be prescribed for patientsvalidation through data comes first. We don't want to step too far off. Were putting one foot in front of the other based on the data, says Alataris. With the increasing rise of scientific misinformation, establishing trust with the public through data is more important than ever.

If Nsos first devices are effective in retraining the brains inflammatory response, it could open the door to a wide range of therapeutic options. More and more conditions, from diabetes to mental health disorders, are being newly understood in the context of inflammation. Indeed, Nesos is already developing two more products to address migraine prevention and postpartum depression.

For Alataris, this is the next level of neuroscience. We are still at the very early stage of what is possible and what we can possibly do. To have these big dreams, you need data to stand on. We dont want to go chasing dragons here, but its a very exciting time, says Alataris. If validated, Nsos technology may be the first step towards a new future of therapeutics.

Im the founder of SynBioBeta, and some of the companies that I write about are sponsors of the SynBioBeta conference and weekly digest, including the Mayfield Fund. Thank you to Desiree Ho for additional research and reporting in this article.

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What If You Could Change Your Immune System By Wearing Earbuds? Meet The Startup That Could Make It Possible - Forbes


Biotechs Developing Innovative Ways to Activate the Immune System Against COVID-19 – BioSpace

Monday, December 14th, 2020

After the initial results of the Pfizer-BioNTech and Moderna vaccines exceeded even the wildest efficacy expectations, one could be forgiven for believing weve found the answer to reclaiming our lives from the grip of COVID-19. In reality, its a little more complicated.

Cases of reinfection are beginning to emerge, showing that protective antibodies may not have the longevity we were hoping for. This poses the question: Is it more important to elicit a robust antibody response, T cell response, or both? Secondly, what is the approach or delivery platform that will achieve the collective robust immune response to finally end the pandemic?

BioSpace spoke with a few companies that have some ingenious ideas at different stages of preclinical and clinical development.

First, Science 101:

The human body contains a B cell responsible for generating and secreting antibodies, which play the important role of blocking viruses. Antibodies do wane, however, and have the potential to become less effective if the virus mutates, which already appears to be happening as cases of COVID-19 reinfection begin to emerge.

Then there are T cells which come in two main types. Helper T cells (CD4+T cells) stimulate the B cells to make antibodies and help killer cells to develop. Killer T cells (CD8+ T-cells) act as a type of clean-up hitter, killing infected host cells and activating other immune cells, enabling viral clearance. Importantly, they can also turn into Memory CD8 T cells which provide a long-lasting immune response.

All of these play a critical role in the adaptive immune system response.

Viral clearance is what is so important to prevent transmission. In my mind, at least, the best way to stop a pandemic is not just to protect the blocking, but to clear the virus if it does get in and reduce transmission, said Dr. Patrick Soon-Shiong, head of NantWorks, the parent company of NantKwest Inc. and ImmunityBio, which are collaborating on a vaccine designed to elicit both an antibody and a T cell response.

Soon-Shiong went on to say that the vaccines currently in late phase development have focused mainly on eliciting a strong antibody response with the Spike (S) protein.

The S protein is the protein that would stimulate an antibody, as well as some level of T cells, but not very strong. The S protein is what every vaccine thats in Phase III right now, Moderna, Pfizer, AstraZeneca, Johnson & Johnson are targeting, because thats the antibody approach, he explained. In fact, none of the phase III protocols actually mention T cells. They do in an exploratory way, but not in a definitive way of measuring the T cells.

The NantKwest and ImmunityBio approach combines the commonly targeted S protein with the lesser known N protein (nucleocapsid protein) which is essential for the virus to survive. They are also using a second-generation adenovirus vector which precludes the possibility of the vaccine becoming ineffective after the first dose, a risk inherent in first-generation adenovirus vector vaccines.

NantKwest Senior Director of Infectious Diseases, Jeffrey Safrit, explained that the nucleocapsid is viewed as a particularly strong stimulator of cellular immunity and improves the generation of memory T cells. T cell mediated immunity has been shown to last significantly longer than antibody-mediated immunity, he added.

In an oft-referenced study published in Nature, Drs. Nina Le Bert and Anthony T. Tan at Duke-NUS Medical School in Singapore showed that patients who recovered from the SARS CoV-1 virus possessed long-lasting memory T cells 17 years after the 2003 outbreak. In addition, the T cells displayed robust cross-reactivity to the N protein of SARS-CoV-2.

This indicates that T cells may just be the ticket to widespread immunity.

The duo announced positive interim safety data from its Phase I dose study on November 10.

Aiming for a More Robust Antibody Response

Abpro Corp., a biotechnology company developing next generation antibody therapies for severe disease, is targeting a more robust antibody response with its therapeutic, ABP 300, which is based on neutralizing monoclonal antibodies.

The company recently completed a Phase 1 study in humans, which will read out in Q1 2021. It also announceddatafrom a challenge study in rhesus monkeyspublished inNature Communications, whichshowed that a single dose of ABP 300 blocks infection of SARS-CoV-2 in prophylactic treatment and clears the virus in three days in a therapeutic setting.

ABP 300 also displayed the potential to neutralize eight SARS-CoV-2 strains with reported high-frequency mutations. This could prove a critical asset in the long-term fight against COVID-19.

Abpro Executive Chairman and Co-Founder Ian Chan said that a neutralizing antibody is exactly the way it sounds. It basically prevents the virus from entering human cells.

Chan further explained that neutralizing antibodies can be an effective one-two punch as both a treatment and a prophylactic.

Neutralizing antibodies have shown that they may be potential first line therapies for mild-to-moderate patients. And then secondly, they can also be used as a preventative type of treatment as well, said Chan.

If someone has not yet received a vaccine or somehow [is] unable to generate an immune response after vaccination and gets infected, then a therapy will be needed. Together, vaccines and therapies will form a potent combination to help mankind get the pandemic under control.

Chan told BioSpace that Abpro would like to get the drug to patients early in 2021.

Targeting the T Cell Response

OSE Immunotherapeutics, a clinical stage biotech focused on controlling the immune system in immuno-oncology and autoimmune diseases, plans to launch the Phase I trial of its vaccine candidate, CoVepiT, in December.

CoVepiT is based on optimized peptides selected to induce a lasting sentinel T lymphocyte immune response against SARS-CoV-2. OSE Chief Scientific Officer, Nicolas Poirier, is adamant about the advantages of his companys T cell specific approach.

We are developing a vaccine that addresses the T cell response only, and the idea, or the advantage, of that strategy is that we are developing a long term or lasting protective response, Poirier said. We can unfortunately expect that the antibody protection will be transient because of what we learned from the past coronavirus infection. And of course, we do not yet have sufficient data from the first-generation vaccines to say that they will be protective from the longer term or midterm.

OSE researchers analyzed more than 46,000 SARS-CoV-2 samples from patients around the world to identify matching vaccine targets. They then compared these samples to SARS-CoV-1 and MERS in order to identify targets that had the best chance of remaining unchanged in the face of mutations or the emergence of another strain.

Preclinical data show that the vaccine activates T memory cell responses. OSE plans to initiate Phase I trials in December and anticipates clinical data early in 2021.

The Combination Approach

Heat Biologics Inc. in collaboration with the University of Miami, is developing a "combination" vaccine that stimulates both antibody and T cell responses. Founder and CEO Jeff Wolf sees the antibody and T cell approaches as a one-two punch to the coronavirus.

Personally, I think you need both, especially in elderly and patients with comorbidities, because these people are really the most impacted by this, Wolf said. I think its clear from the data thats out there, you have patients who have generated a robust antibody response and then they come down with a severe case of COVID months later. So even though people think they have protection, they really dont.

Heats vaccine works by engineering multiple protein regions of the SARS-CoV-2 virus into its proprietary gp96 platform to create combined antibody and T cell immunity. When delivered to the body through the vaccines cells, the gp96 protein is then able to show the SARS-CoV-2 proteins to the immune system in a powerful way that activates a power T cell response.

Heat has previously used the go96 platform in preclinical studies against Simian immunodeficiency virus (SIV), HIV, and the Zika virus.

In terms of long term immunity against SARS-CoV-2, only time will tell what the magic ingredients turn out to be, but when it comes to a deadly pandemic that has killed more than 1.4 million people globally and more than 260,000 in the U.S. alone, the verdict is clear: we need to cover all our bases with all of our antibodies and T cells on board.

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