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Archive for the ‘Immune System’ Category

How Do Our Immune Systems Develop in the First Days of Life? – Technology Networks

Sunday, October 25th, 2020

Within the womb, a human fetus benefits from the protection of the placenta, limiting their contact with pathogens. However, once born, babies face a myriad of germs completely new to their bodies. Their immune system must rapidly develop to ensure early protection from infection. But what is exactly the dynamic of the immune system development in the first days of life?

To answer this question researchers from the Precision Vaccines Program at Boston Children's Hospital received funding from the Human Immunology Project Consortium (HIPC)/National Institute of Allergy and Infectious Diseases (NIAID) to study the timing of activation of different components of the immune system during the first week of life. For the first time, they observe an acute immune response starting right after the birth, followed by the progressive increase in key factors of innate immunity.

"Our study has revealed the developmental changes of the immune system during the defining first 7 days of life, in two independent cohorts. Furthermore, we provide insights into the development of the immune system which appears to be initiated by immunological triggers associated with birth" says Dr Hanno Steen lead author of the study published in the open-access journal Frontiers in Immunology.

The researchers studied the inventory of proteins present in newborn blood plasma, in two independent cohorts in The Gambia (West Africa) and in Papua New Guinea (PNG), at birth and after the first, third, and seventh day of life. This approach enabled them to follow, with high sensitivity, the dynamic of immune components in the blood across the first week of human life.

Firstly, the team observes, right after birth, an increase of plasma proteins involved in an acute inflammatory response, suggesting an activation of the immune system development. This is followed by an increase of components related to an innate immunity pathway called the complement system, starting as early as 24h after birth. The complement pathway has a major role in innate immunity, through the recruitment of several complexes of proteins (C1 to C9) it can induce direct destruction of pathogens. Furthermore, as the majority of the complement proteins are increasing concentrations of complement inhibitors is decreasing, until a new increase on day seven. Finally, the analysis also reveals that antibodies transmitted by the mother are declining rapidly over the first week of life while antibodies related to the complement pathway activation (IgM and IgG1) increase. Altogether, these results suggest that the complement pathway could have a central role in neonatal immunity and could be an important defense mechanism against pathogens in infancy.

A better understanding of the immune system and its development during the first week of life is particularly important given the prevalence of infections in early life. Neonatal infections cause 700,000 annual deaths, representing 40% of mortality in children under five years of age. "Having a better understanding of the immune system at the beginning of life will be pivotal for the development of precision vaccines for the newborns, which is one of the major goals of the Precision Vaccines Program at Boston Children's Hospital" says Steen.

ReferenceBjerg Bennike T et al/ Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life. Frontiers Immunology. Accessed October 22, 2020.https://doi.org/10.3389/fimmu.2020.578505

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Body’s immune response drives production of non-functional coronavirus ‘gateway protein’: Study – The Tribune India

Sunday, October 25th, 2020

London, October 25

Some immune system molecules trigger the production of a non-functional variant of the human protein used by the novel coronavirus to enter and infect host cells, according to a study that sheds light on the body's natural defence against COVID-19.

The research, published in the journal Nature Genetics, examined the genetic information that codes for the ACE2 receptor, to which the SARS-CoV-2 virus must bind in order to enter and infect human cells.

In the study, scientists, including those from the Francis Crick Institute in London, analysed existing genetic databases and human cells to identify a new variant, or isoform, of ACE2 called MIRb-ACE2, which the SARS-CoV-2 virus cannot bind to.

"This variant of genetic information is the result of retroelements in our DNA, which can 'jump' around the genome impacting gene expression," said Kevin Ng, a co-author of the study from the Francis Crick Insitute.

"From looking at which other species also have this variant, it appears to be widely present in mammals, so it must have entered the human genome a long time ago," he added.

In order to understand the role this variant plays in the body's immune response to SARS-CoV-2, the scientists assessed the effects of exposing cells to interferons -- signalling proteins that are made and released by virus-infected cells.

They found that interferons increase the response and production specifically of MIRb-ACE2, while ACE2 is not affected.

According to the researchers, the findings allay concerns that interferon-based treatments for SARS-CoV-2 could inadvertently be helping the virus by bringing about an increase in coronavirus cell receptors in the body.

They said the coronavirus is not able to bind to MIRb-ACE2, which is also highly unstable.

"The non-functional MIRb-ACE2 isoform was likely responsible for results from previous studies that suggested interferons could be upregulating ACE2, as there was no distinction between these two isoforms," said George Kassiotis, another co-author of the study.

"This highlights how scientific knowledge about SARS-CoV-2 is constantly being revised and updated as new research is carried out. We still have a lot to learn, but we are making rapid progress," Kassiotis said.

The researchers also found that cells in the upper aero-digestive tract, including the mouth and the nose, express more MIRb-ACE2 than the functional ACE2, and this balance changes lower in this tract and in the intestines.

They believe more research is needed to understand why this difference occurs and the impact it might have on how the virus spreads in the body. PTI

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Daycares in Finland Built a ‘Forest Floor’, And It Changed Children’s Immune Systems – ScienceAlert

Sunday, October 25th, 2020

Playing through the greenery and litter of a mini forest's undergrowth for just one month may be enough to change a child's immune system, according to a small new experiment.

When daycare workers in Finland rolled out a lawn, planted forest undergrowth such as dwarf heather and blueberries, and allowed children to care for crops in planter boxes, the diversity of microbes in the guts and on the skin of young kids appeared healthier in a very short space of time.

Compared to other city kids who play in standard urban daycares with yards of pavement, tile and gravel, 3-, 4-, and 5-year-olds at these greened-up daycare centres in Finland showed increased T-cells and other important immune markers in their blood within 28 days.

"We also found that the intestinal microbiota of children who received greenery was similar to the intestinal microbiota of children visiting the forest every day," saysenvironmental scientist Marja Roslund from the University of Helsinki.

One daycare before (left) and after introducing grass and planters (right). (University of Helsinki)

Prior research has shown early exposure to green space is somehow linked to a well-functioning immune system, but it's still not clear whether that relationship is causal or not.

The experiment in Finland is the first to explicitly manipulate a child's urban environment and then test for changes in their micriobiome and, in turn, a child's immune system.

While the findings don't hold all the answers, they do support a leading idea - namely that a change in environmental microbes can relatively easily affect a well-established microbiome in children, giving their immune system a helping hand in the process.

The notion that an environment rich in living things impacts on our immunity is known as the 'biodiversity hypothesis'. Based on that hypothesis,a loss of biodiversity in urban areascould be at least partially responsible for the recent rise in immune-related illnesses.

"The results of this study support the biodiversity hypothesis and the concept that low biodiversity in the modern living environment may lead to an un-educated immune system and consequently increase the prevalence of immune-mediated diseases," the authors write.

The study compared the environmental microbes found in the yards of 10 different urban daycares looking after a total of 75 kids between the ages of 3 and 5.

Some of these daycares contained standard urban yards with concrete and gravel, others took kids out for daily nature time, and four had their yards updated with grass and forest undergrowth.

Over the proceeding 28 days, kids in these last four daycares were given time to play in their new backyard five times a week.

When researchers tested the microbiota of their skin and gut before and after the trial, they found improved results compared to the first group of kids that played in daycares with less greenery for the same amount of time.

Even in that short duration of the study, researchers found microbes on the skin and guts of children who regularly played in green spaces had increased in diversity - a feature which is tied to an overall healthier immune system.

Their results largely matched the second group of kids at daycares who had outings for daily nature time.

Among kids who got outside, playing in the dirt, the grass and among the trees, an increase in a microbe called gammaproteobacteria appeared to boost the skin's immune defence, as well as increase helpful immune secretions in the blood and reduce the content of interleukin-17A, which is connected to immune-transmitted diseases.

"This supports the assumption that contact with nature prevents disorders in the immune system, such as autoimmune diseases and allergies," says Sinkkonen.

The results aren't conclusive and they will need to be verified among larger studies around the world. Still, the benefits of green spaces appear to go beyond our immune systems.

Researchshows getting outside is also good for a child's eyesight, and being in nature as a kid is linked to better mental health. Some recent studies have even shown green spaces are linked to structural changes in the brains of children.

What's driving these incredible results is not yet clear. It could be linked to changes to the immune system, or something about breathing healthy air, soaking in the sun, exercising more or having greater peace of mind.

Given the complexities of the real world, it's really hard to control for all the environmental factors that impact our health in studies.

While rural children tend to have fewer cases of asthma and allergies, the available literature on the link between green spaces and these immune disorders is inconsistent.

The current research has a small sample size, only found a correlation, and can't account for what children were doing outside daycare hours, but the positive changes seen are enough for scientists in Finland to offer some advice.

"It would be best if children could play in puddles and everyone could dig organic soil," encouragesenvironmental ecologist Aki Sinkkonen, also from the University of Helsinki.

"We could take our children out to nature five times a week to have an impact on microbes."

The changes are simple, the harms low, and the potential benefits widespread.

Bonding with nature as a kid is also good for the future of our planet's ecosystems.Studiesshow kids who spend time outdoors are more likely to want to become environmentalists as adults, and in a rapidly changing world, that's more important than ever.

Just make sure everyone's up to date on their tetanus vaccinations, Sinkkonen advises.

The study was published in the Science Advances.

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COVID-19 causes some patients’ immune systems to attack their own bodies, which may contribute to severe illness – The Conversation US

Sunday, October 25th, 2020

Across the world, immunologists who retooled their labs to join the fight against SARS-CoV-2 are furiously trying to explain why some people get so sick while others recover unscathed. The pace is dizzying, but some clear trends have emerged.

One area of focus has been the production of antibodies powerful proteins capable of disabling and killing invading pathogens like viruses. Of great concern has been the sporadic identification of so-called autoreactive antibodies that, instead of targeting disease causing microbes, target the tissues of individuals suffering from severe cases of COVID-19.

Early studies implicated these autoantibodies in dangerous blood clots forming in patients admitted to intensive care. More recently, they have been linked to severe disease by inactivating critical components of viral immune defenses in a significant fraction of patients with severe disease.

As an immunologist within the Lowance Center for Human Immunology at Emory University, I have been investigating the immune response responsible for producing antibodies in COVID-19. Under the direction of Dr. Ignacio Sanz, our group has previously investigated immune responses contributing to autoantibody production in autoimmune disorders like lupus, and more recently in severe cases in COVID-19. However, while we were able to characterize the response in COVID-19 patients as autoimmunelike, we could not confirm the production of autoantibodies hidden within their antiviral responses.

Now we can.

In a newly released study awaiting peer-review, we describe the alarming finding that in the sickest patients with COVID-19, autoantibody production is common a finding with large potential impact on both acute patient care and infection recovery.

Autoantibodies come in flavors that are usually associated with specific disease types. Patients with lupus, for example, will often have antibodies that target their own DNA the molecules that make up the human genome.

Patients with the autoimmune disorder rheumatoid arthritis are less likely to have those antibodies, but more likely to show positive tests for rheumatoid factor antibodies that target other antibodies.

In this study, the Lowance Center group analyzed the medical charts of 52 patients in intensive care who were diagnosed with COVID-19. None of them had a history of autoimmune disorders. However, they were tested during infection for autoantibodies found in a variety of disorders.

The results are stark. More than half of the 52 patients tested positive for autoantibodies. In patients with the highest levels of c-reactive protein (a marker of inflammation) in the blood, more than two-thirds displayed evidence that their immune system was producing antibodies attacking their own tissue.

While these findings raise concerns, there are things that our data dont reveal. Although patients with severe disease clearly display autoantibody responses, the data dont tell us to what extent these autoantibodies contribute to the most severe symptoms of COVID-19.

It could be that severe viral illness routinely results in the production of autoantibodies with little consequence; this could just be the first time were seeing it. We also dont know how long the autoantibodies last. Our data suggest that they are relatively stable over a few weeks. But, we need follow-up studies to understand if they are persisting routinely beyond infection recovery.

Importantly, we believe that the autoreactive responses we have identified here are specific to the SARS-CoV-2 infection there is no reason to believe that similar results would be expected through vaccination against the virus.

However, while it is possible that these autoantibodies are benign, or even helpful in a yet-unidentified manner, its also possible that they arent. Maybe these self-targeted antibody responses do indeed contribute to disease severity, helping explain the delayed onset of severe symptoms in some patients that may correlate with antibody production.

This could be a reason that treatment with dexamethasone, an immunosuppressant often used to quell flare-ups of autoimmune disorders, might be effective in treating patients with only the most severe disease. It is also possible that these responses are not short lived, outlasting the infection and contributing to ongoing symptoms now experienced by a growing number of long-hauler COVID-19 patients.

Most concerning, it is possible that these responses could self-perpetuate in some patients, resulting in the emergence of new, permanent autoimmune disorders.

My colleagues and I sincerely hope that this is not the case rather, that the emergence of autoantibodies in these patients is a red herring, a quirk of a viral immune response in some patients that will resolve on its own. But we need to do better than hope we need to ask the right questions and figure out the answers. Fortunately, this study also gives us the tools to do that.

The tests that were run on these patients to determine their autoreactive profile are not specialized. They are available to most hospital labs across the country. Indeed, the two most common antibodies that we find in these patients, antinuclear antibodies and rheumatoid factor, are detected by common tests used by rheumatologists.

Our study shows that by testing for just these two autoantibodies, and the inflammatory marker c-reactive protein, we may be able to identify patients more likely to be experiencing potentially dangerous immune responses that might benefit from more aggressive immune modulation.

[Get facts about coronavirus and the latest research. Sign up for The Conversations newsletter.]

Further, autoreactivity testing might help identify patients who might benefit from rheumotological follow-up to monitor recovery, and help us understand whether some cases of long-hauler COVID-19 might be related to persisting autoantibodies. If so, these patients might respond to the same immune-targeted therapies that have been successful in MIS-C where autoantibody production has now been documented.

Finally, by testing patients immediately following COVID-19 recovery, we can establish baselines and begin to track the possible emergence of new cases of autoimmunity following this terrible disease, and plan early rheumatological intervention if needed.

We now have the tools. Its time to start using them.

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Strengthen your immune system against Covid with help of Vitamin D, zinc and pickles – Mirror Online

Sunday, October 25th, 2020

Winter is coming and a second wave of Covid-19 is already with us, so it has never been more important to strengthen your immunity.

Along with hand-washing, masks and social distancing, its the best defence we have against the coronavirus.

A vaccine is still some way off and scientists warn that without one there is no hope of achieving the herd immunity needed to end the pandemic.

Boosting your own immunity makes sense, and studies show there is lots you can do.

A balanced diet is key, but there are certain nutrients that are particularly important and scientists have been working hard to find the stars that can help in the Covid battle.

Take these simple steps to strengthen your immune system and keep you well through the tough winter ahead:

Vitamin D, which is essential for healthy bones and muscles, is often known as the sunshine vitamin giving a big clue as to why we dont get enough in winter.

While it can be found in some foods, including oily fish, red meat and eggs, our bodies grab the majority of what they need from exposure to sunlight.

One in five Brits is deficient, with the number increasing as the nights draw in.

And thats why the official advice is to consider taking a supplement containing 10mcg of vitamin D (the equivalent of 400IU) during winter.

But as well as keeping bones strong, this simple vitamin could also play a key role in the fight against Covid-19.

A super-study published earlier this year, which analysed results from 39 trials, found that taking 10mcg of the sunshine vitamin reduced the risk of respiratory infections by up to 23 per cent.

More recently, researchers at the University of Birmingham, who tested blood samples from 392 healthcare staff, found that 72per cent of those who were deficient in vitamin D had also caught Covid-19.

By contrast, only 51 per cent of those with good levels carried antibodies confirming they had been infected.

Covidence-UK, a study that uses monthly surveys of UK citizens to identify potential risk factors for Covid-19, has also identified a link.

Researchers are launching a randomised control trial to see if providing free vitamin D to people with low levels reduces their odds of catching the virus. To sign up and support the Covidence-UK search for ways to reduce the risk of Covid-19, visit qmul.ac.uk/covidence.

Some scientists believe its no accident that countries where cabbage and fermented vegetables, such as sauerkraut and kimchi, are popular, have reported lower coronavirus death rates.

Dr Jean Bousquet, Honorary Professor of Pulmonary Medicine at Montpellier University, France, has calculated that every gram of fermented vegetables eaten each day reduces the risk of dying of Covid-19 by 35 per cent.

A similar pattern was seen in countries where a lot of cabbage is consumed, and Professor Bousquet believes the benefits are down to high levels of the antioxidant sulforaphane in them.

He adds: Nutrition may play a role in the immune defence against Covid and may explain some of the differences seen in Covid across Europe. Ive now changed my diet, and it includes raw cabbage three times a week, sauerkraut once a week and pickled vegetables.

Dozens of studies have underlined the importance of zinc for strong immunity. And the World Health Organisation confirms it, saying: Zinc is thought to help decrease susceptibility to acute lower respiratory tract infections by regulating various immune functions.

Zinc can be found in shellfish, beans and lentils, but eight per cent of adults here in the UK do not get the recommended intake.

Research has shown that taking zinc within 24 hours of cold symptoms appearing cuts the duration of infections by a third.

Excitingly, studies have confirmed zinc inhibits Covid-19 and there is evidence it may boost levels of interferon, a protein that helps our immune system identify threats.

The balance of good and bad bacteria in our gut has a big impact on immunity. Dr Bousquets research has also identified a link between fermented dairy products, such as yoghurt and kefir, and a lower rate of deaths from the virus.

A recent Chinese study discovered that probiotic drinks that contained a combination of lactobacillus bacteria reduced the risk of respiratory infections by 59 per cent.

Another study, published in the European Journal of Public Health, found that children who were given daily probiotic supplements werearound a third less likely to needantibiotics.

A 150ml glass of orange juice provides more than 80 per cent of the immune-strengthening vitamin C that we need each day.

But there is growing scientific interest around another nutrient in orange juice, which could be even more important for our immunity.

Hesperidin, a micronutrient found in citrus fruit, slows the rate that viruses can replicate. Laboratory tests showed such strong antiviral activity that some scientists think it could be used to develop new drugs against dreaded influenza.

A recent study showed it locks on to key proteins on the Covid-19 virus, which could make it harder for infection to take hold.

Because the highest concentrations are found in the pith of fruit, juice will have more hesperidin in it than whole fruit. Shop-bought orange juice contains three times more hesperidin than juice squeezed at home.

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Immunity Boosting Is Over, Its All About Balance – British Vogue

Sunday, October 25th, 2020

Immune boosting is a phrase that I really cant get along with, says leading nutritional therapist and healthy eating expert, Amelia Freer, when asked about the best immune-boosting advice for the coming winter months. In fact, according to Freer, weve been approaching it all wrong and when it comes to our immune system, the aim isnt to boost, but rather to balance it.

Read more: Feeling Low? Here Are 8 Ways To Ease Seasonal Affective Disorder

An overactive immune system can result in auto-immune disease, or a significant widespread inflammatory state, while an under-active or otherwise compromised immune system can increase our risk of infection neither of which is ideal. In the simplest of terms, says Freer, we want to be able to switch our immune function on appropriately, and then switch it off again when the infection risk has passed.

As for how we can do this best, Freer suggests nurturing and supporting our overall health and wellbeing. There are various nutrients that our body requires to mount and suppress an appropriate immune response, she comments. The best way to get these is through eating a balanced, nutritious, and abundant diet, so including a wide variety of different whole foods into our diets throughout the winter is a great place to start.

A variety of fresh green vegetables is key.

SCIENCE PHOTO LIBRARY

First up is dark-green vegetables such as kale, chard, spinach, rocket, Brussels sprouts, sprouting broccoli. They all provide a variety of beneficial phytonutrients, fibre, vitamin A, magnesium, folate and more. If there is one thing to add to our diets, it is this group of vegetables. Aim for at least one portion per day (remembering that when cooked, they tend to shrink considerably in terms of volume, making it easier to achieve this target).

Citrus fruits are a good source of vitamin C and perfect for the coldest winter months a little bit of concentrated sunshine just when we need it most. I particularly love the month or two that blood oranges are available [around December to April] I have one almost every day when I can, as the most deliciously simple dessert.

Citrus fruits such as oranges, grapefruits, and mandarins can provide, a little bit of concentrated sunshine just when we need it most, according to Freer.

voloshin311

This is a cheap and readily available oily fish and a source of long-chain omega-3 fatty acids, which can help to regulate inflammation in the body. It also contains some food-based vitamin D, as well as protein, and its a great speedy choice for lunches. Top tip: look out for unsmoked, frozen mackerel fillets in the freezer section of some supermarkets. Ive found that its the best fish to cook from frozen, and contains less salt than the smoked version.

There are a huge variety of orange-fleshed pumpkins to enjoy over winter. They provide a source of vitamin A, which, as a fat-soluble vitamin, is best absorbed alongside some healthy fats. I therefore tend to slow-roast my squash and pumpkins in a little olive oil, and then enjoy as they come, blended into sauces or soups, or tossed into salads with rocket, radicchio, some toasted hazelnuts and crumbled feta.

Brazil nuts are a key source of the micronutrient selenium, which is an important mineral for optimal immune response. Just four or five Brazil nuts per week can meet our selenium requirements. It is, however, one of the few whole food nutrients that we can over-consume, so its best to mix things up and eat just a few each week alongside a variety of other nuts and seeds, too.

Protein and pulses are important for enabling the body to mount an appropriate immune response.

Adl Bkefi

I adore pulses in all shapes and sizes, and I find them a convenient source of protein I aim to have roughly a palm-sized portion of protein at each meal of the day. Protein is important for enabling the body to mount an appropriate immune response, as well as for repair and growth of our bodys tissues, and for appetite and blood-sugar regulation. I buy pulses in bulk in jars and add them to soups, make them into hummus and other dips, throw them into curries and stews, or eat them cold with some olive oil, lemon and a few chopped herbs.

Shellfish is a good source of zinc and vitamin B12, and mussels and scallops are in season over the winter months. They are a bit of a treat, but its worth making the effort to cook them once in a while. Do check that they are sustainably sourced and if youre unsure about cooking them yourself, it might be a good option to consider ordering if eating out.

Rolled oats are a great choice and can provide not only a warming and delicious porridge breakfast, but also a hefty dose of fibre, too. Soaking oats overnight can help to make the nutrients they contain more absorbable, as well as speeding up the cooking time.

Eating eggs regularly is a simple way to introduce immunity balancing benefits into your diet.

Jody Louie took this picture

Eggs are such a versatile and useful ingredient to have on hand for quick meals and speedy snacks. They are also a source of vitamin B12, a little vitamin D, vitamin A, protein and some are even fortified with omega-3 fatty acids, all of which are important for balanced immune function.

Maintaining a good level of hydration can help to keep our mucosal barriers moist, such as those in our mouth and the lining of our nose. This might sound strange, but hydration of these tissues helps to support the natural immune function that exists within them, warding off infection before it has a chance to enter the body. Plus water wont spoil your appetite for the abundance of nourishing whole foods awaiting you at your next meal.

Good hydration supports muscles and skin tissues, enabling them to better fight off infection.

Dulin

The only supplement that is recommended for everyone to consider over the winter months is vitamin D. In some countries, the sunlight is not strong enough between October and early March for our skin to make enough vitamin D to meet our requirements.

I know its been said a thousand times before, but it really is what works: wash your hands, prioritise sleep, actively respond to and manage stress, move regularly, exercise, moderate alcohol and avoid smoking. Its not original, but it is effective.

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Increased Humoral Immune Response Against C. Diff Toxins Linked to Mild Disease – MD Magazine

Sunday, October 25th, 2020

Findings from a new study showed an association between high serum immunoglobulin G (IgG) and immunoglobulin A (IgA) levels and milder cases of Clostridium difficile (C. difficile).

Specifically, this association was modulated by the two serum antibodies targeting of both toxins A (TcdA) and B (TcdB), which play an essential role in the pathogenesis of the disease.

Investigators from Tel Aviv University and Tel Aviv Sourasky Medican Center conducted a case-control study to determine the risk factors of C. difficile infection (CDI) and evaluate the link between humoral immune response and CDI severity.

Thus, their analysis consisted of a total of 50 patients with CDI, 62% of whom were female. This represented a subset of 140 total CDI patients who were enrolled in their study.

They categorized CDI patients according to severitysevere disease was defined as leukocytosis with a white blood cell count of 15,000 cells/L, decreased blood albumin (<30 g/L) or a rise in serum creatinine level 1.5 times the premorbid level. Any patient who did not fulfill any of these requirements were considered to have a mild case.

Additionally, they analyzed 52 patient controls who were not suffering from diarrhea, where 56% were female. In total, they had enrolled 140 controls.

Both CDI patients and controls were matched by age, sex, hospitalization ward (medical or surgical), and number of hospitalization stays.

The mean age between the CDI and control groups were 79.2% years and 82.7%, respectively.

The investigators collected stool specimens from the both groups to test for C. difficile. Blood samples were also collected, and the levels of serum IgG and IgA antibodies against TcdA and TcDB were measured.

Overall, they found that patients with CDI presented with higher geometric mean titers (GMT) values of serum IgG antibody against TcdA when compared with the control group (20.1 EU vs 11.6 EU, respectively; P = .0001).

The GMT values of serum IgG against TcdB were also higher for the CDI group than for the control (18.0 EU vs 12.0 EU, respectively; P = .04).

They also noted that similar trends were observed for IgA antibodies, but the differences were not statistically significant.

In terms of associations for C. diff severity, they found that GMT values of serum IgA against TcdB was significantly higher among CDI patients with mild disease as compared with patients with severe disease (9.2 EU vs 4.9 EU, respectively; P = .023).

Similar but non-statistically significant trends were noted found for IgA and IgG levels against TcdA, as well as for IgG against TcdB.

Limiting the analysis to sera that were collected at days 714 following the diagnosis of C. difficile showed significantly higher IgG levels against TcdA and TcdB in patients with mild CDI compared to patients with severe CDI, they wrote.

Furthermore, they found significant correlations between serum IgG levels and TcdA and TcdB (Spearmans r = 0.31). Other strong correlations included IgA levels against TcdA and TcDB (r = 0.53) and IgG and IgA levels against TcdB (r = 0.43).

Although there remains great uncertainty behind the mechanism that can explain the protective effect of serum IgA and IgG antibodies against C. diff toxins, the investigators nonetheless suggested implications for the findings.

Based on the current evidence from observational studies and our new findings, the concept of presenting antigens that can prime or boost the immune system towards the production of antitoxin circulating antibodies seems a sensible approach for developing preventive and therapeutic vaccines and technologies for CDI, the team wrote.

The study, "Enhanced Humoral Immune Responses against Toxin A and B of Clostridium difficile is Associated with a Milder Disease Manifestation," was publshed online in Journal of Clinical Medicine.

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Dr Todd Rice Explains the Anti-inflammatory Benefits of Vitamin D to Our Immune Systems – AJMC.com Managed Markets Network

Sunday, October 25th, 2020

We are still working to figure out why low levels of vitamin D are associated with worse outcomes in critical illness, noted Todd W. Rice, MD, FCCP, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee.

Studies have shown that low levels of vitamin D are associated with worse outcomes in critical illnessfor instance, needing to be in the intensive care unit (ICU) morebut we are still working to figure out why, noted Todd W. Rice, MD, FCCP, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee, in an interview for this years CHEST Annual Meeting.

Transcript

Tell us about your presentation on day 1 of CHEST, Vitamin D in Critical Illness: Helpful Fact or Hopeless Fiction.

This is a presentation in a session about vitamins and vitamins in the ICU. And obviously, based off of the title, Im going to talk about vitamin D. The short, brief story of vitamin D is that weve had a number of studies that have shown that low levels of vitamin D are associated with worse outcomes, including needing to be into the ICU more, having more infections in the ICU, and staying in the ICU longer, having higher mortality while youre in the ICU. And so the thought process is that repleting peoples vitamin D to normal levels may prevent some of these bad outcomes. And weve tried this in a number of trials and we havent had great success in improving outcomes by giving patients vitamin D. And the question then becomes, why is that the case? Is it that low vitamin D level is not the reason that people do worse, its just kind of associated with being sick and doing worse? Or is there something about vitamin D metabolism and vitamin D absorption that we dont yet understand? So were not really supplementing it right, were not really targeting the right levels, those sorts of things. And I think were still working to figure that out.

How do the pleiotropic effects of micronutrients affect critical illness?

Vitamin D has a number of kind of positive effects in the body. Obviously, its involved in bone metabolismthats probably not that relevant in critical illnessbut its very, very, very much involved in the immune system. And its sort of a cofactor for our immune cells in fighting infection. And its been shown in a number of other studies, not in the ICU, that low vitamin D levels result in less robust immune systems, more prone to get infections, and worse outcomes.

The other effects of it are that it seems to have some anti-inflammatory effects. We dont entirely understand exactly how it decreases inflammation, but it seems to decrease inflammation and also kind of has some effects on the endothelial lining of the lungs and the vasculature. So all of those effects kind of together are pleiotropic in the fact that they sort of grow these areas, stimulate these areas, and are beneficial to the body in that regard.

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Will masks become the ‘new normal’ even after the pandemic has passed? Some Americans say so – CNBC

Sunday, October 25th, 2020

People wear face masks in Times Square as the city continues the re-opening efforts following restrictions imposed to slow the spread of coronavirus on October 22, 2020 in New York City.

Noam Galai | Getty Images

Mandy Elmore, 47, has been wearing masks for more than 20 years. That's because she has cystic fibrosis, a hereditary disease that affects her lungs and digestive system.

Because of her illness, a cold or flu can land her in the hospital. Prior to the pandemic, Elmore, who lives in Dallas, Texas, had to stop going to church or traveling on planes to avoid strangers coughing and sneezing directly on her.

"Masks offer freedom for those of us who are sick," she said. "I would feel comfortable going to church in the winter or to movies or to birthday parties if people could think about those like me who truly suffer as a result of a simple cold virus."

For millions of Americans like Elmore, it would change their lives for the better if it became more of a cultural norm in the U.S. for people to wear masks when they're under the weather or in crowded areas. The West has stigmatized mask-wearing, but in countries like Japan or South Korea, residents might get dirty looks if they hop on a subway with a sniffle and no mask.

Still, there's reason for skepticism. Not everyone in America is wearing masks, even now, when public health officials are strongly encouraging them to do so. Rallies to protest masks have popped up across the country, with many Americans pointing out that it's a violation of their personal freedoms.

But for others, who potentially represent a less vocal majority, it could become the new normal. Since the start of the pandemic, many people bought a handful of masks for the first time and have gotten used to wearing them in public. Doctors and public health experts believe that American culture could fundamentally shift to embrace new hygiene practices.

"I think we do need a new culture of masks, at least any time not feeling well, and I think masks are in and handshakes out for the indefinite future," said Dr. Tom Frieden, the former director of the C.D.C. during the Obama Administration and the president of global health initiative Resolve to Save Lives.

"Post pandemic, there will be new social norms," added Dr. Panagis Galiatsatos, a pulmonary and critical care doctor, who treats patients with chronic respiratory conditions like COPD and cystic fibrosis, as well as Covid-19.

"I think face masks will continue to be used by the general public in times when they don't feel well, and honestly we're realizing that no one feels slighted without a handshake," he said.

Sometimes, it takes a pandemic to change behavior. Across East Asia, mask wearing really took off in the aftermath of the SARS outbreak in 2003. The U.S. was largely spared from SARS. But in Hong Kong, where more than 280 people died, there was widespread panic. All of that led to many countries developing practices around how to tamp down on potential disease outbreaks early, with measures like social distancing, travel bans, and masks.

Almost two decades later, this advanced planning gave the region an edge when it came to Covid-19. Many people already had a mask or two at home and had become used to wearing one. In countries like Taiwan, those who did not wear a mask were occasionally even publicly shamed on social media for failing to take proper precautions.

William Hsiao, emeritus professor of economics inthe Department of Health Policy and Management at the Harvard T.H. Chan School of Public Health, told CNBC that in these cultures, there's a strong feeling that sometimes people have to sacrifice their "individual desires and benefits" for the sake of their community. That helped countries like Taiwan and Vietnam, which have experienced relatively few cases of Covid-19, come together to face a threat in a more unified way. In Taiwan, only 7 people have died from the virus, while Vietnam has reported just 35 deaths.

In the West, it hasn't been as easy to disseminate public health measures. Not all Americans have eagerly embraced mask-wearing, even in the height of the pandemic. Research organizations like Brookings say that "a culture of individualism" is an obstacle. Americans aren't as used to putting the needs of the community ahead of themselves.

Still, some Americans say their perspective has fundamentally shifted. Rather than powering through illness by going to school or work as normal, they say they'd take extra precautions or stay home. And some say that they'd be comfortable wearing a mask in a crowded setting from now on.

"I grew up going to school, even if I was sick" said Spencer Guthrie, 45, from San Francisco. "I never missed a single day of school from K-12."

But Guthrie said his views have changed since the start of the pandemic. He would take greater precautions now if he felt under the weather. "Masks are not the slightest bit inconvenient for long periods of time if you find one that fits well," he said.

Others say they discovered unexpected benefits to wearing a mask. Hope King, a New York-based journalist, has found comfort in that moment on the street when people pull their mask up as they approach. She sees it as a sign of respect.

King has experienced the rise of anti-Asian racism during the pandemic. So wearing a mask makes her feel safer.

"I think maybe you can't tell immediately that I'm Asian from far away, especially if I'm wearing glasses," she said.

King envisions keeping her mask on as long as people around her continue to do so. She also plans to wear one if she starts to feel sick, as a signal to others that she's invested in protecting them.

For some young Americans, wearing a mask just isn't big deal. Gurdane Bhutani, 29, suspects that face coverings won't be perceived as a "strange thing to do" in the future at times when people are packed together. He already refrains from eating peanuts on an airplane in case someone has an allergy. So a mask doesn't seem any different.

"It's not hard to do, and it could make a difference for someone else," he said. "I know people with autoimmune conditions are feeling really relieved that everyone is wearing masks now."

Doctors like Krishna Komanduri, chief of the division of transplantation and cellular therapy at the University of Miami, has noticed an increased empathy for immunocompromised patients in recent months. People with weakened immune systems have long feared getting sick and that prospect is never far from their thoughts.

And now, with Covid-19, even young and healthy people are concerned about avoiding germs and spreading illness.

"For our cancer patients, nothing has really changed," he said. "Rather we have been drawn into their world."

Cancer patients, he said, or really anyone with a compromised immune system, are no strangers to masks and social distancing. Some received strange looks prior to the pandemic, he said. But not anymore. "More widespread adoption of these measures would be good in general," he explained.

For her part, Elmore, who suffers from cystic fibrosis, has never felt safer. And ironically, that's during a respiratory pandemic.

"Now, if someone coughs or sneezes with a mask on in the store, I'm not trying to run to get away," she said. "Pre-Covid, I would literally breathe out and walk as fast as possible to get away from the airflow."

Elmore said her entire family would keep their ears alerted for any hint of sickness at a time when very few people wore masks. "My husband used to say, 'cougher on the left,' to prevent me from breathing as they walked by," she said.

Elmore isn't expecting that everyone will wear masks at all times in the future. She is hoping that people will take more precautions, however, when they start feeling sick. "I do hope those that are having symptoms will consider them," she said.

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MSK-led Studies Support the Concept of Cancer Environment Immunotherapy – On Cancer – Memorial Sloan Kettering

Sunday, October 25th, 2020

Summary

Two MSK-led studies published in the journal Nature support the idea of using immunotherapy drugs to treat the environment surrounding a tumor as an indirect way to combat cancer.

Despite the remarkable successes of immune-based treatments for cancer, not everyone responds to these approaches, and relapses do occur. Researchers around the world are racing to find ways to improve outcomes for people receiving immunotherapy. But new findings from scientists at Memorial Sloan Kettering suggest they may be focusing too narrowly on the problem.

According to Ming Li, an immunologist in the Sloan Kettering Institute, most existing immunotherapy approaches, including both checkpoint blockade and CAR T therapy, aim to prod the immune system into finding and killing cancer cells a kind of frontal attack on the disease.

But tumors also need supportive environments safe harbors in which to grow and thrive. They need the support of blood vessels that provide them with nutrients, Dr. Li says.

Could destroying these safe harbors be an indirect way to fight this internal enemy? Dr. Li thinks the answer is yes, and on October 21, he published two papers in the journal Nature in support of the concept.

We know that the immune system is incredibly adept at recognizing harmful invaders and attacking them with precision, he says. But thats not the only way our immune system protects us from threats. It also promotes healing of damaged tissue so that pathogens cant take root in the body. This latter role, we now show, can also be enlisted in the fight against cancer.

Dr. Li and his colleagues found they could thwart cancers in mice by encouraging immune cells to begin the process of wound repair around a tumor. In the process, blood vessels that feed the cancer are pruned away and cancer cells starve and die. Its an approach that Dr. Li has dubbed cancer environment immunotherapy.

To understand how wound healing can help curb cancer, consider what happens when someone gets an injury, say a cut from a knife. Early on, the site becomes inflamed red, hot, and swollen. During this phase of wound healing, blood vessels dilate and immune cells rush in to fight enemies that may cause infection and clean up the debris. But later on, the wound fills in with new tissue, and inflammation resolves.

An important player in the wound healing process is a molecule called TGF-beta, whose presence waxes and wanes with the inflammation cycle. In the context of a cancerous wound, TGF-beta persists and makes cancer growth worse. By contrast, blocking its action inhibits tumor development. This latter effect is dependent upon immune cells called T cells, previous research has shown.

Blocking the action of a molecule called TGF-beta in immune cells (right) triggers cell death (blue) in tumors in mice.

Dr. Li and his team wanted to find out more about which T cells were involved in curbing cancer growth when TGF-beta is blocked. They initially suspected that a subset of T cells called CD8 T cells, or killer T cells, were responsible for restraining tumor development. But when they genetically removed the receptor for TGF-beta from CD8 cells in mice, it had no effect on cancer growth.

Next, they asked whether a different subset of T cells, called CD4 T cells, or helper T cells, could explain the phenomenon of cancer suppression. Indeed, genetically removing the receptor for TGF-beta in CD4 T cells dramatically reduced cancer growth in mice.

How do CD4 T cells contribute to cancer control in this context? Dr. Li and his colleagues found that these cells promote wound healing around a tumor. As part of this process, the blood vessels supplying nutrients to a tumor are dramatically remodeled, and a kind of protective wall is formed around the tumor, depriving it of sustenance.

These results, reported in the first Nature paper, showed that blocking TGF-beta signaling in CD4 T cells could activate a powerful wound healing response that directly opposes cancer development.

But what about tumors that have already been growing? Could blocking TGF-beta restrain them? Dr. Li and his team explored this question in a second set of experiments, published in a second Nature article.

By blocking TGF-beta inhelper T cells, we allow the wound healing to run to completion. We heal the wound that is cancer.

They designed an antibody-based drug that can bind to both TGF-beta andhelper T cells. They found that this drug, which they called 4T-Trap, could dramatically reduce cancer in mice.

Previous attempts at blocking TGF-beta as a cancer treatment have not been successful, likely because this molecule has many effects in the body, and therefore blocking it completely can cause severe side effects such as heart problems or even the appearance of new cancers. But 4T-Trap targets the TGF-beta-blocking-molecule directly to CD4 T cells, so side effects are reduced. In other words, its a more targeted approach.

That fact that CD4helper T cells were the key players rather than CD8 killer T cells came as something of a surprise to the researchers. These days, CD8 cytotoxic T cells that recognize cancer cells are in the spotlight. Dr. Li says, Its almost become dogma that if its T cell mediated, then it must be CD8 T cells. That was our original hypothesis, too. But that turns out not to be the case.

Yet the findings are not completely unprecedented. In fact, the discovery that the promotion of wound healing can dramatically curb cancer progression meshes nicely with older work. In the mid-1980s, cancer researcher Harold Dvorak published a now-famous article in the New England Journal of Medicine, in which he argued that tumors are essentially wounds that do not heal. Tumors enlist normal wound healing to help themselves grow. They thrive by enlisting the early stages of the immune responses to tissue damage growth of new blood vessels, for example but then never get to later stages of wound healing when these blood vessels are normally pruned away.

By blocking TGF-beta inhelper T cells, we allow the wound healing to run to completion, Dr. Li says. We heal the wound that is cancer.

Reflecting on the way his results echo these earlier findings, Dr. Li says, Its an exciting homecoming.

He proposes that such cancer environment immunotherapy could be a powerful addition to current immune-based treatments for cancer. His lab is currently collaborating with physician-researchers at MSK to translate these new findings to patients.

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What We Know So Far about How COVID Affects the Nervous System – Scientific American

Sunday, October 25th, 2020

Many of the symptoms experienced by people infected with SARS-CoV-2 involve the nervous system. Patients complain of headaches, muscle and joint pain, fatigue and brain fog, or loss of taste and smellall of which can last from weeks to months after infection. In severe cases, COVID-19 can also lead to encephalitis or stroke. The virus has undeniable neurological effects. But the way it actually affects nerve cells still remains a bit of a mystery. Can immune system activation alone produce symptoms? Or does the novel coronavirus directly attack the nervous system?

Some studiesincluding a recent preprint paper examining mouse and human brain tissueshow evidence that SARS-CoV-2 can get into nerve cells and the brain. The question remains as to whether it does so routinely or only in the most severe cases. Once the immune system kicks into overdrive, the effects can be far-ranging, even leading immune cells to invade the brain, where they can wreak havoc.

Some neurological symptoms are far less serious yet seem, if anything, more perplexing. One symptomor set of symptomsthat illustrates this puzzle and has gained increasing attention is an imprecise diagnosis called brain fog. Even after their main symptoms have abated, it is not uncommon for COVID-19 patients to experience memory loss, confusion and other mental fuzziness. What underlies these experiences is still unclear, although they may also stem from the body-wide inflammation that can go along with COVID-19. Many people, however, develop fatigue and brain fog that lasts for months even after a mild case that does not spur the immune system to rage out of control.

Another widespread symptom called anosmia, or loss of smell, might also originate from changes that happen without nerves themselves getting infected. Olfactory neurons, the cells that transmit odors to the brain, lack the primary docking site, or receptor, for SARS-CoV-2, and they do not seem to get infected. Researchers are still investigating how loss of smell might result from an interaction between the virus and another receptor on the olfactory neurons or from its contact with nonnerve cells that line the nose.

Experts say the virus need not make it inside neurons to cause some of the mysterious neurological symptoms now emerging from the disease. Many pain-related effects could arise from an attack on sensory neurons, the nerves that extend from the spinal cord throughout the body to gather information from the external environment or internal bodily processes. Researchers are now making headway in understanding how SARS-CoV-2 could hijack pain-sensing neurons, called nociceptors, to produce some of COVID-19s hallmark symptoms.

Neuroscientist Theodore Price, who studies pain at the University of Texas at Dallas, took note of the symptoms reported in the early literature and cited by patients of his wife, a nurse practitioner who sees people with COVID remotely. Those symptoms include sore throat, headaches, body-wide muscle pain and severe cough. (The cough is triggered in part by sensory nerve cells in the lungs.)

Curiously, some patients report a loss of a particular sensation called chemethesis, which leaves them unable to detect hot chilies or cool peppermintsperceptions conveyed by nociceptors, not taste cells. While many of these effects are typical of viral infections, the prevalence and persistence of these pain-related symptomsand their presence in even mild cases of COVID-19suggest that sensory neurons might be affected beyond normal inflammatory responses to infection. That means the effects may be directly tied to the virus itself. Its just striking, Price says. The affected patients all have headaches, and some of them seem to have pain problems that sound like neuropathies, chronic pain that arises from nerve damage. That observation led him to investigate whether the novel coronavirus could infect nociceptors.

The main criteria scientists use to determine whether SARS-CoV-2 can infect cells throughout the body is the presence of angiotensin-converting enzyme 2 (ACE2), a protein embedded in the surface of cells. ACE2 acts as a receptor that sends signals into the cell to regulate blood pressure and is also an entry point for SARS-CoV-2. So Price went looking for it in human neurons in a study now published in the journal PAIN.

Nociceptorsand other sensory neuronslive in discreet clusters, found just outside the spinal cord, called dorsal root ganglia (DRG). Price and his team procured nerve cells donated after death or cancer surgeries. The researchers performed RNA sequencing, a technique to determine which proteins a cell is about to produce, and they used antibodies to target ACE2 itself. They found that a subset of DRG neurons did contain ACE2, providing the virus a portal into the cells.

Sensory neurons send out long tendrils called axons, whose endings sense specific stimuli in the body and then transmit them to the brain in the form of electrochemical signals. The particular DRG neurons that contained ACE2 also had the genetic instructions, the mRNA, for a sensory protein called MRGPRD. That protein marks the cells as a subset of neurons whose endings are concentrated at the bodys surfacesthe skin and inner organs, including the lungswhere they would be poised to pick up the virus.

Price says nerve infection could contribute to acute, as well as lasting, symptoms of COVID. The most likely scenario would be that the autonomic and sensory nerves are affected by the virus, he says. We know that if sensory neurons get infected with a virus, it can have long-term consequences, even if the virus does not stay in cells.

But, Price adds, it does not need to be that the neurons get infected. In another recent study, he compared genetic sequencing data from lung cells of COVID patients and healthy controls and looked for interactions with healthy human DRG neurons. Price says his team found a lot of immune-system-signaling molecules called cytokines from the infected patients that could interact with receptors on neurons. Its basically a bunch of stuff we know is involved in neuropathic pain. That observation suggests that nerves could be undergoing lasting damage from the immune molecules without being directly infected by the virus.

Anne Louise Oaklander, a neurologist at Massachusetts General Hospital, who wrote a commentary accompanying Prices paper in PAIN, says that the study was exceptionally good, in part because it used human cells. But, she adds, we dont have evidence that direct entry of the virus into [nerve] cells is the major mechanism of cellular [nerve] damage, though the new findings do not discount that possibility. It is absolutely possible that inflammatory conditions outside nerve cells could alter their activity or even cause permanent damage, Oaklander says. Another prospect is that viral particles interacting with neurons could lead to an autoimmune attack on nerves.

ACE2 is widely thought to be the novel coronaviruss primary entry point. But Rajesh Khanna, a neuroscientist and pain researcher at the University of Arizona, observes that ACE2 is not the only game in town for SARS-CoV-2 to come into cells. Another protein, called neuropilin-1 (NRP1), could be an alternate doorway for viral entry, he adds. NRP1 plays an important role in angiogenesis (the formation of new blood vessels) and in growing neurons long axons.

That idea came from studies in cells and in mice. It was found that NRP1 interacts with the viruss infamous spike protein, which it uses to gain entry into cells. We proved that it binds neuropilin and that the receptor has infectious potential, says virologist Giuseppe Balistreri of the University of Helsinki, who co-authored the mouse study, which was published in Sciencealong with a separate study in cells. It appears more likely that NRP1 acts as a co-factor with ACE2 than that the protein alone affords the virus entry to cells. What we know is that when we have the two receptors, we get more infection. Together, its much more powerful, Balistreri adds.

Those findings piqued the interest of Khanna, who was studying vascular endothelial growth factor (VEGF), a molecule with a long-recognized role in pain signaling that also binds to NRP1. He wondered whether the virus would affect pain signaling through NRP1, so he tested it in rats in a study that was also published in PAIN. We put VEGF in the animal [in the paw], and lo and behold, we saw robust pain over the course of 24 hours, Khanna says. Then came the really cool experiment: We put in VEGF and spike at the same time, and guess what? The pain is gone.

The study showed what happens to the neurons signaling when the virus tickles the NRP1 receptor, Balistreri says. The results are strong, demonstrating that neurons activity was altered by the touch of the spike of the virus through NRP1.

In an experiment in rats with a nerve injury to model chronic pain, administering the spike protein alone attenuated the animals pain behaviors. That finding hints that a spike-like drug that binds NRP1 might have potential as a new pain reliever. Such molecules are already in development for use in cancer.

In a more provocative and untested hypothesis, Khanna speculates that the spike protein might act at NRP1 to silence nociceptors in people, perhaps masking pain-related symptoms very early in an infection. The idea is that the protein could provide an anesthetic effect as SARS-CoV-2 begins to infect a person, which might allow the virus to spread more easily. I cannot exclude it, says Balistreri. Its not impossible. Viruses have an arsenal of tools to go unseen. This is the best thing they know: to silence our defenses.

It still remains to be determined whether a SARS-CoV-2 infection could produce analgesia in people. They used a high dose of a piece of the virus in a lab system and a rat, not a human, Balistreri says. The magnitude of the effects theyre seeing [may be due to] the large amount of viral protein they used. The question will be to see if the virus itself can [blunt pain] in people.

The experience of one patientRave Pretorius, a 49-year-old South African mansuggests that continuing this line of research is probably worthwhile. A motor accident in 2011 left Pretorius with several fractured vertebrae in his neck and extensive nerve damage. He says he lives with constant burning pain in his legs that wakes him up nightly at 3 or 4 A.M. It feels like somebody is continuously pouring hot water over my legs, Pretorius says. But that changed dramatically when he contracted COVID-19 in July at his job at a manufacturing company. I found it very strange: When I was sick with COVID, the pain was bearable. At some points, it felt like the pain was gone. I just couldnt believe it, he says. Pretorius was able to sleep through the night for the first time since his accident. I lived a better life when I was sick because the pain was gone, despite having fatigue and debilitating headaches, he says. Now that Pretorius has recovered from COVID, his neuropathic pain has returned.

For better or worse, COVID-19 seems to have effects on the nervous system. Whether they include infection of nerves is still unknown like so much about SARS-CoV-2. The bottom line is that while the virus apparently can, in principle, infect some neurons, it doesnt need to. It can cause plenty of havoc from the outside these cells.

Read more about the coronavirus outbreak from Scientific American here. And read coverage from our international network of magazines here.

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Protein that Keeps Immune System from Freaking Out Could Form Basis for New Therapeutics – UC San Diego Health

Sunday, October 18th, 2020

The immune response to infections is a delicate balance. We need just enough action to clear away the offending bacteria or viruses, but not so much that our own bodies suffer collateral damage.

Macrophages are immune cells at the front line, detecting pathogens and kicking off an inflammatory response when needed. Understanding how macrophages determine when to go all-out and when to keep calm is key to finding new ways to strike the right balance particularly in cases where inflammation goes too far, such as in sepsis, colitis and other autoimmune disorders.

Two macrophages (blue) fighting to engulf the same pathogen (green). GIV/Girdin is shown in red.

In a study published October 14, 2020 in the Proceedings of the National Academy of Sciences, researchers at University of California San Diego School of Medicine discovered that a molecule called Girdin, or GIV, acts as a brake on macrophages.

When the team deleted the GIV gene from mouse macrophages, the immune cells rapidly overacted to even small amounts of live bacteria or a bacterial toxin. Mice with colitis and sepsis fared worse when lacking the GIV gene in their macrophages.

The researchers also created peptides that mimic GIV, allowing them to shut down mouse macrophages on command. When treated with the GIV-mimic peptide, the mices inflammatory response was tempered.

When a patient dies of sepsis, he or she does not die due to the invading bacteria themselves, but from an overreaction of their immune system to the bacteria, said senior author Pradipta Ghosh, MD, professor at UC San Diego School of Medicine and Moores Cancer Center. Its similar to what were seeing now with dangerous cytokine storms that can result from infection with the novel coronavirus SARS-CoV-2. Macrophages, and the cytokines they produce, are the bodys own immune-stimulating agents and when produced in excessive amounts, they do more harm than good.

Digging deeper into the mechanism at play, Ghosh and team discovered that the GIV protein normally cozies up to a molecule called Toll-like receptor 4 (TLR4). TLR4 is stuck right through the cell membrane, with bits poking inside and outside the cell. Outside of the cell, TLR4 is like an antenna, searching for signs of invading pathogens. Inside the cell, GIV is nestled between the receptors two feet. When in place, GIV keeps the feet apart, and nothing happens. When GIV is removed, the TLR4 feet touch and kick off a cascade of immune-stimulating signals.

Ghoshs GIV-mimicking peptides can take the place of the protein when its missing, keeping the feet apart and calming macrophages down.

We were surprised at just how fluid the immune system is when it encounters a pathogen, said Ghosh, who is also director of the Institute for Network Medicine and executive director of the HUMANOID Center of Research Excellence at UC San Diego School of Medicine. Macrophages dont need to waste time and energy producing more or less GIV protein, they can rapidly dial their response up or down simply by moving it around, and it appears that such regulation happens at the level of gene transcription.

Ghosh and team plan to investigate the factors that determine how the GIV brake remains in place when macrophages are resting or is removed to mount a response to a credible threat. To enable these studies, the Institute for Network Medicine at UC San Diego School of Medicine recently received a new $5 million grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Ghosh shares this award with her colleagues Debashis Sahoo, PhD, assistant professor at UC San Diego School of Medicine and Jacobs School of Engineering, and Soumita Das, PhD, associate professor of pathology at UC San Diego School of Medicine.

Co-authors of the study include: Lee Swanson, Gajanan D. Katkar, Julian Tam, Rama F. Pranadinata, Yogitha Chareddy, Jane Coates, Mahitha Shree Anandachar, Vanessa Castillo, Joshua Olson, Victor Nizet, Irina Kufareva, Soumita Das, all at UC San Diego.

Funding for this research came, in part, from the National Institutes for Health (grants AI141630, AI155696, CA100768, CA160911, DK107585, UL1TR001442, DK 0070202), DiaComp and Helmsley Charitable Trust.

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What We Know And Don’t Know About COVID-19 Reinfection Cases – ScienceAlert

Sunday, October 18th, 2020

As President Trump claims that he is immune to COVID-19 and isolated reports emerge of reinfection, what is the truth about immunity to COVID-19?

To date, there have been six published cases of COVID-19 reinfection, with various other unverified accounts from around the world. Although this is a comparably small fraction of the millions of people known to have been infected, should we be concerned? To unpick this puzzle, we must first consider what we mean by immunity.

When we are infected with any pathogen, our immune system quickly responds to try to contain the threat and minimise any damage. Our first line of defence is from immune cells, known as innate cells. These cells are not usually enough to eliminate a threat, which is where having a more flexible "adaptive" immune response comes into play our lymphocytes.

Lymphocytes come in two main varieties: B lymphocytes, which make antibodies, and T lymphocytes, which include cells that directly kill the germy invaders.

As antibodies are readily measured in blood, they are often used to indicate a good adaptive immune response. However, over time, antibodies levels in our blood wane, but this doesn't necessarily mean protection is lost. We retain some lymphocytes that know how to deal with the threat our memory cells. Memory cells are remarkably long-lived, patrolling our body, ready to spring into action when needed.

Vaccines work by creating memory cells without the risk of a potentially fatal infection. In an ideal world, it would be relatively easy to create immunity, but it's not always that straightforward.

Although our immune system has evolved to deal with a huge variety of pathogens, these germs have also evolved to hide from the immune system. This arms race means that some pathogens such as malaria or HIV are very tricky to deal with.

Infections that have spilled over from animals - zoonotic diseases - are also challenging for our immune system because they can be completely novel. The virus that causes COVID-19 is such a zoonotic disease, originating in bats.

COVID-19 is caused by a betacoronavirus. Several betacoronaviruses are already common in the human population most familiar as a cause of the common cold. Immunity to these cold-causing viruses isn't that robust but immunity to the more serious conditions, Mers and Sars, is more durable.

Data to date on COVID-19 shows that antibodies can be detected three months after infection, although, as with Sars and Mers, antibodies gradually decrease over time.

Of course, antibody levels are not the only indication of immunity and don't tell us about T lymphocytes or our memory cells. The virus causing COVID-19 is structurally similar to Sars, so perhaps we can be more optimistic about a more durable protective response time will tell. So how worried then should we be about reports of reinfection with COVID-19?

The handful of case reports on reinfection with COVID-19 don't necessarily mean that immunity is not occurring. Issues with testing could account for some reports because "virus" can be detected after infection and recovery. The tests look for viral RNA (the virus's genetic material), and viral RNA that cannot cause infection can be shed from the body even after the person has recovered.

Conversely, false-negative results happen when the sample used in testing contains insufficient viral material to be detected for example, because the virus is at a very low level in the body. Such apparent negative results may account for cases in which the interval between the first and second infection is short. It is hugely important, therefore, to use additional measures, such as viral sequencing and immune indicators.

Reinfection, even in immunity, can happen, but usually this would be mild or asymptomatic because the immune response protects against the worst effects. Consistent with this is that most verified cases of reinfection reported either no or mild symptoms. However, one of the latest verified cases of reinfection which happened just 48 days after the initial infection actually had a more severe response to reinfection.

What might account for the worse symptoms the second time round? One possibility is the patient did not mount a robust adaptive immune response first time round and that their initial infection was largely contained by the innate immune response (the first line of defence). One way to monitor this would be to assess the antibody response as the type of antibody detected can tell us something about the timing of infection. But unfortunately, antibody results were not analysed in the recent patient's first infection.

Another explanation is that different viral strains caused the infections with a subsequent impact on immunity. Genetic sequencing did show differences in viral strains, but it isn't known if this equated to altered immune recognition. Many viruses share structural features, enabling immune responses to one virus to protect against a similar virus. This has been suggested to account for the lack of symptoms in young children who frequently get colds caused by betacoronaviruses.

However, a recent study, yet to be peer-reviewed, found that protection against cold-causing coronaviruses did not protect against COVID-19. In fact, antibodies recognising similar viruses can be dangerous accounting for the rare phenomenon of antibody-dependent enhancement of disease (ADE). ADE occurs when antibodies enhance viral infection of cells with potentially life-threatening consequences.

It should be emphasised, though, that antibodies are only one indicator of immunity and we have no data on either T lymphocytes or memory cells in these cases. What these cases emphasise is a need to standardised approaches in order to capture the critical information for robust evaluation of the threat of reinfection.

We are still learning about the immune response to COVID-19, and every piece of new data is helping us unpick the puzzle of this challenging virus. Our immune system is a powerful ally in the fight against infection, and only by unlocking it can we ultimately hope to defeat COVID-19.

Sheena Cruickshank, Professor in Biomedical Sciences, University of Manchester.

This article was originally published byThe Conversation. Read the original article.

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Boost your immune system with THESE 5 healthy juice recipes shared by Nutritionist Arooshi Agarwal – PINKVILLA

Sunday, October 18th, 2020

Having healthy juices is an easy and effective way to enhance your immunity to combat all diseases and infections. Here are 5 juice recipes from Arooshi Agarwal, Nutritionist and founder of Arooshis Nutrylife to amp up your immune system.

Our immune system works constantly without a pause and so it requires the best fuel for its performance in figuring out which cells belong to our body and which doesnt. These internal little wonderful warriors (antibodies) that protect us from diseases, infections, and what not needs ultimate care so that we are kept healthy and strong from inside. The immune system doesnt only need the right conditions to perform but also requires the right nutrition.

The current global crisis has made us realize the importance of immunity in our daily lives. Good immunity wont come easy without taking care of the gut (small intestine) and liver health. More than 70% of our immune system is in our gut which forms a foundation of our overall health. These two are one of the most important organs in our body that ensures the immunity that we need in our daily life to combat all sorts of illnesses. Having different types of juice is one of the most effective ways to boost our immune system. Hence, Arooshi Aggarwal, nutritionist and founder of Arooshis Nutrylife, shares some easy juice recipes.

5 juice recipes shared by nutritionist Arooshi Agarwal.

Green Juice

Green juice is a powerhouse of supplements for a solid immune system. It works best for detoxifying the liver.You need Wheat Grass, bottle gourd, a handful of mint leaves, and lime. Do not add salt or any condiments, try taking it raw. Blend these green veggies. You can adjust the consistency either with water or coconut water. The ideal time to consume this juice is in the morning.This juice is packed with antioxidants, iron, potassium magnesium which have a nerve and muscle relaxing effect. This juice helps in reducing the inflammation, cools down the body heat and antioxidants help in building up the antibodies.

White Juice

For this juice, you will need bottle gourd, green apple, celery and ginger. Ginger has always been the go-to food for colds. This is because it kills rhinovirus, the infectious agent responsible for the common cold. Celery is filled with sodium, a natural electrolyte that helps to treat dehydration. Green apples are also rich in vitamin C that boosts our immunity. Blend these together with water and drink.

Orange juice

For orange juice, you will be needing carrots, pumpkin, and apricots. This juice is rich in Vitamin A which is also fat-soluble vitamin and helps us fight against eye infections and provides a better vision.

Red juice

For this refreshing juice, you will need beetroot, tomato, ginger, garlic, and turmeric. These are wonder veggies to improve immunity. These veggies keep gut flora (good bacteria) healthy and improve gut health. Not only this juice refreshes the mood but also helps to treat influenza, runny nose, and body aches. This juice is so healthy that it calms down the symptoms of Rheumatoid Arthritis as turmeric, garlic, and ginger have strong inflammatory effects.

Yellow juice

For this, you will need pineapple, carrot mint leaves and lemon. This juice is loaded with immunity builders. It helps in treating cold, cough, and sore throat. Pineapple can reduce the bronchial inflammation which provides better respiration and relieves from the excess mucus formation. This juice is high on Vitamin C, vitamin A, iron, potassium, and antioxidants which also benefit the skin and hair health.

Remember

These five juices will be a blessing to your immune system and vital organs. Also remember, hydration, exercise, and a healthy diet play a very important role to keep your immune system up. While juicing may benefit your physical health, it is equally important to take care of your mental health. A healthy mind resides in a healthy body and vice versa!

Also Read:Significance of self screening in early detection of Breast Cancer explained by Dr Chandrani Mallik

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Protein That Pumps the Brakes on Macrophages in Immune Overreaction – Genetic Engineering & Biotechnology News

Sunday, October 18th, 2020

At the front line of our immune system macrophages are standing by, detecting pathogens and kicking off an inflammatory response when needed. Understanding how these immune cells know when to go all-out and when to keep calm is critical to finding new ways to strike the right chord in cases where the immune system overreacts, such as in sepsis and other autoimmune disorders.

Researchers at the University of California (UC) San Diego School of Medicine report they have discovered a protein that acts as a brake on macrophages. Their findings, TLR4 signaling and macrophage inflammatory responses are dampened by GIV/Girdin, were published in the Proceedings of the National Academy of Sciences.

Sensing of pathogens by Toll-like receptor 4 (TLR4) induces an inflammatory response; controlled responses confer immunity but uncontrolled responses cause harm. Here we define how a multimodular scaffold, GIV, or Girdin, titrates such inflammatory response in macrophages, noted the researchers.

When the team deleted the GIV gene from mouse macrophages, the immune cells overreacted to small amounts of live bacteria. Mice with colitis and sepsis fared worse when lacking the GIV gene in their macrophages. They also created peptides that mimic GIV, which allowed them to put the brakes on mouse macrophages on command. When treated with the GIV-mimic peptide, the mices inflammatory response was tempered.

When a patient dies of sepsis, he or she does not die due to the invading bacteria themselves, but from an overreaction of their immune system to the bacteria, explained Pradipta Ghosh, MD, professor at UC San Diego School of Medicine and Moores Cancer Center. Its similar to what were seeing now with dangerous cytokine storms that can result from infection with the novel coronavirus SARS-CoV-2. Macrophages, and the cytokines they produce, are the bodys own immune-stimulating agents and when produced in excessive amounts, they do more harm than good.

Further observation revealed that the GIV protein works together with TLR4. Outside of the cell, TLR4 is like an antenna, searching for signs of invading pathogens. Inside the cell, GIV waits between the receptors two feet. When in place, GIV keeps the feet apart, and nothing happens. When GIV is removed, the TLR4 feet touch and sends off immune-stimulating signals.

We were surprised at just how fluid the immune system is when it encounters a pathogen, said Ghosh, who is also director of the Institute for Network Medicine and executive director of the HUMANOID Center of Research Excellence at UC San Diego School of Medicine. Macrophages dont need to waste time and energy producing more or less GIV protein, they can rapidly dial their response up or down simply by moving it around, and it appears that such regulation happens at the level of gene transcription.

The researchers are looking forward to investigating the factors that determine how the GIV brake remains in place when macrophages are resting or is removed to mount a response to a credible threat. The Institute for Network Medicine at UC San Diego School of Medicine recently received a $5 million grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Ghosh shares this award with her colleagues Debashis Sahoo, PhD, assistant professor at UC San Diego School of Medicine and Jacobs School of Engineering, and Soumita Das, PhD, associate professor of pathology at UC San Diego School of Medicine.

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Why is coronavirus killing more men than women? – theday.com

Sunday, October 18th, 2020

Early in the coronavirus outbreak, hospital data from China revealed a startling disparity: COVID-19, the disease caused by the virus, was killing far more men than women.

That difference persisted in other Asian countries, such as South Korea, as well as in European countries, such as Italy. Then, it appeared in the United States.

By mid-October, the coronavirus had killed almost 17,000 more American men than women, according to data from the Centers for Disease Control and Prevention. For every 10 women claimed by the disease in the United States, 12 men have died, found an analysis by Global Health 50/50, a U.K.-based initiative to advance gender equality in health care.

That disparity was one of many alarming aspects of the new virus. It bewildered those unfamiliar with the role of gender in disease.

But the specialized group of researchers who study that relationship was not surprised. It prepared an array of hypotheses. One possible culprit was male behavior. Perhaps men were more likely to be exposed to the virus due to social factors; a disproportionately male workforce, for instance, could place more men in contact with infected people. Or men's lungs might be more vulnerable because they were more likely to smoke in the earliest countries to report the differences.

What has become more evident, 10 months into this outbreak, is that men show comparatively weaker immune responses to coronavirus infections, which may account for those added deaths.

"If you look at the data across the world, there are as many men as women that are infected. It's just the severity of disease that is stronger in most populations in men," Franck Mauvais-Jarvis, a Tulane University physician who studies gender differences in such diseases as diabetes. In such cases, biology can help explain why.

- The male immune response. Women generally have stronger immune systems, thanks to sex hormones, as well as chromosomes packed with immune-related genes. About 60 genes on the X chromosome are involved in immune function, Johns Hopkins University microbiologist Sabra Klein told The Washington Post in April. People with two X chromosomes can benefit from the double helping of some of those genes.

Akiko Iwasaki, who studies immune defenses against viruses at Yale University, wanted to see how sex differences might play out in coronavirus infections. She and her colleagues cast a proverbial net into the immune system to fish out schools of microscopic fighters.

"We did a holistic look at everything we can measure immunologically," Iwasaki said, listing a litany of the molecules and cells that form the body's bulwark against pathogens: "cytokines, chemokines, T cells, B cells, neutrophils. Everything that we had access to."

In male patients, the T-cell response was weaker, the scientists found. Not only do T cells detect infected cells and kill them, they also help direct the antibody response. "It's like a master regulator of immune response. And when you have a drop in T cells, or in their ability to become activated, you basically lose the conductor of an orchestra," Iwasaki said.

The power of the immune system wanes as people age, regardless of sex. But what is a gentle decline for women is an abrupt dive off a cliff for men: Iwasaki's work indicates the T-cell response of men in their 30s and 40s is equivalent to that of a woman in her 90s.

And T cells aren't the only immune feature disproportionately impaired in men. Another paper, published in September in PLOS Biology, examined anonymous human genetic material collected along with viruses in nasal swabs.

That study found throttled defense signals in men. When a cell detects a virus, it performs the molecular equivalent of yanking the fire alarm, said one of the study's author, Nicole Lieberman, a research scientist at the University of Washington. That alarm is manifest in genetic messengers, called RNA, which react almost immediately.

The reaction should cause cells to churn out the first lines of defense, such as interferons, immune system molecules that, as the name suggests, interfere with the virus's ability to reproduce. Other molecules summon specialized immune cells to destroy the pathogens. "You want the fire alarm to go off for long enough that you can get the fire department there," Lieberman said.

Lieberman and her co-authors, however, found that in men and some older populations, the fire alarm shuts off early - maybe even before the firefighters have arrived. "That, I think, is the functional consequence, potentially, of what we're seeing here," she said.

- Harmful autoantibodies. Not only is the immune system in men weaker, but in some severe cases of the coronavirus, it may hobble itself. A study of nearly 1,000 patients with life-threatening COVID-19, published in Science in September, found evidence of molecular self-sabotage. Immune system fighters were acting against the body's defenses, like rebellious castle guards splintering their own gates. This flaw was much more prevalent in men than women.

Specifically, the researchers detected what are called autoantibodies, molecules that bind and neutralize parts of the immune system. Those neutralizers disabled a subset of defender molecules known as type-1a interferon. Simply put, having autoantibodies led to more viral replication.

Ninety-five of 101 people with autoantibodies against interferon were male. "Somehow males are probably more prone to develop such autoantibodies, but we do not know why," said study author Petter Brodin, a pediatrician at Sweden's Karolinska Institute who studies the immune system.

Interferon molecules come in several types, so it's possible these patients could be treated with another flavor of interferon, Brodin said. But that may be difficult, he acknowledged, because interferons are most helpful early in the course of an infection, before the disease progresses to life-threatening stages.

The lack of killer T cells, coupled with neutralizing antibodies, is "like a double whammy," Iwasaki said, "that would then ultimately increase the viral load in these men."

What's unusual about this result is that most autoantibody immune disorders appear in women, as is the case with the chronic disease lupus.

Iwasaki's research is examining whether female immune systems may play a role in people with long-lasting COVID-19, nicknamed long-haulers.

"There are thousands of people suffering from chronic symptoms," which may be debilitating, Iwasaki said. Many long-haulers are young and the majority of them, though not all, are women.

- Men behaving differently.

Beyond these biological differences, it would be simplistic to ignore how gender's other aspects, such as behavior and social norms, may also influence the pandemic.

Broadly speaking, men may be less likely to be worried about COVID-19 than women, fitting the pattern that women generally treat health risks more seriously. Women took a more cautious approach to the disease, a recent poll found, expressing more concern they could return to workplaces safely. Women are also more likely to follow expert advice such as mask-wearing and social distancing, according to another study that included surveys and observations of pedestrians' behavior in New York, Connecticut and New Jersey.

Sarah Hawkes, a professor of global public health at University College London who, with her husband, co-directs Global Health 50/50, said that the image of men as risk-takers extends back hundreds of years to John Graunt, one of the first people to participate in the field now known as epidemiology.

After he reviewed England's death records, Graunt postulated in 1662 that "men, being more intemperate then women, die as much by reason of their Vices" - that is, male behavior was to blame. Hawkes argues that "350 years later," Graunt's point still stands. "It is undoubtedly a mixture of both biology and behavior" responsible for the health differences in men and women, she said.

The share of coronavirus deaths in women also rises with their share of the full-time workforce, according to a report by University of Oxford economist Renee Adams that used Global Health 50/50 data.

"The more you have women participating in the workforce, the smaller your sex difference becomes," Hawkes said. That lines up with gender inequalities - men are more likely to work in environments where they are exposed to air pollution and other harms, Hawkes said. When women start to enter those traditionally masculine spaces, she said, it "turns out, women can get as sick as men."

The gender disparities discovered in the response to COVID-19 have sparked a surge of interest in such differences more broadly. "Almost nobody, apart from the people working in the field, were interested in that difference between men and women in disease until February or March," when the first results showed that more men were dying, Mauvais-Jarvis said.

Even agencies at the forefront of public health, such as the CDC, were initially slow to reveal sex-disaggregated coronavirus data, Hawkes said. The U.K. public health surveillance system was similarly late. Hawkes took those delays as a sign of just how unimportant people considered this data, since it is so readily available: When people die, their death certificates state whether they were male, female or, in some places, nonbinary.

The CDC data finally made that information accessible in mid-April. The male-skewed patterns revealed in those deaths conform to what was seen in earlier outbreaks of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), both within the family of coronaviruses. And it is in line with other viral responses. "We know that women develop much better antibody response to flu vaccines," Iwasaki said.

Some of those experts are hoping to capitalize on this moment to shine a spotlight on other gender differences in health. The coronavirus, after all, isn't the only problem to afflict men and women unequally - so, too, do cancer, asthma, heart disease and other common illnesses, as Mauvais-Jarvis noted in a recent paper in the Lancet.

"The kinds of differences that we're seeing and outcomes in COVID-19 are not unexpected. They're not exceptional," Hawkes said. If there's surprise, it only demonstrates the widespread underestimation of the differences in men and women that persist even among physicians, she said.

Mauvais-Jarvis referred to this faulty approach as "bikini medicine" - in which clinicians view female patients as interchangeable with male ones, except for the organs covered by swimwear.

The coronavirus has helped accelerate the trend away from that outdated view. The "one positive that's come out of the pandemic," Hawkes said, is the sudden realization that gendered social factors and biology "may have a relationship with your life expectancy, your experience with illness, your risk of illness. It has made that conversation a little bit more real."

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Factor D: Is blocking this protein the key to stopping COVID-19 from damaging organs? – CTV News

Saturday, October 17th, 2020

TORONTO -- While scientists race to develop a safe and effective vaccine to prevent the spread of COVID-19, researchers at Johns Hopkins University have focused on preventing severe organ damage from patients own immune systems by inhibiting an important protein.

The team from the universitys school of medicine sought to better understand how SARS-CoV-2, the virus that causes COVID-19, attacks the body and causes severe inflammatory responses in certain individuals.

The studys senior author, Dr. Robert Brodsky, director of the hematology division at the Johns Hopkins University School of Medicine, explained that their research focused on an integral part of the immune system called the innate immune system or the complement system.

This is really our first defence against a lot of bacteria and viruses, he told CTVNews.ca during a telephone interview from Baltimore, Md. on Thursday.

The complement system enhances, or complements, the ability of antibodies and phagocytic cells to clear pathogens from the body. This system consists of more than 30 proteins, including two factor H and factor D that were of particular interest to the research team.

Factor H is a control protein that regulates the chemical signals that trigger inflammation and the immune system.

Its what allows the complement system to fight off foreign organisms, but not destroy host tissues, Brodsky explained.

Factor D is another protein in the complement system that is immediately upstream from factor H in the chain of immune events triggered by the virus.

During an infection of SARS-CoV-2, the famous spike proteins on the surface of the virus, which make it resemble a medieval mace, allow it to attach to healthy cells in the human body. In order to do this, the spikes latch on to heparan sulfate a large sugar molecule found on the surface of cells in the lungs, blood vessels, and smooth muscle of most organs.

Just binding to heparan sulfate, [the virus] probably couldnt get into the cell and start replicating. But without heparan sulfate, there wouldnt be enough of it to get to the ACE-2 receptor, he said.

There has been a lot of attention given to the role of the ACE-2 receptor protein (angiotensin-converting enzyme 2) and its role as an entry point for the coronavirus to infect a range of human cells.

However, Brodsky said the ACE-2 receptor isnt on all tissues, which is why his team focused on how the coronavirus binds to the heparan sulfate molecule instead.

Heparan sulfate is pretty much on every cell, just about every cell in the body, he said.

Returning to factor H, the researchers found that when the SARS-CoV-2 virus binds with the cells heparan sulfate sugar molecule, it occupies the site where the factor H protein would normally attach to protect that cell from the bodys immune response.

Without this protection, cells in the lungs, heart, kidneys and other organs can be destroyed by the defence mechanism nature intended to safeguard them, the researchers said.

To prevent the virus from occupying factor Hs spot on cells and leaving vital organs vulnerable to the bodys immune response, the academics attempted to stop that sequence of events from occurring at all by inhibiting factor D.

As previously mentioned, factor D is located directly upstream from factor H in the complement system. By blocking the function of factor D, the sequence of immune events triggered by the invading virus will also be stopped.

To simplify, Brodsky compared the complement systems immune response to a car in motion.

The viral spike proteins disable the biological brakes, factor H, enabling the gas pedal, factor D, to accelerate the immune system and cause cell, tissue and organ devastation. Inhibit factor D, and the brakes can be reapplied and the immune system reset, he explained.

In the lab, the research team used a small molecule in a complement-inhibiting drug to block factor D and the chain of events leading to the immune systems attack on the bodys healthy cells.

While the drug hasnt been approved by the U.S. Food and Drug Association (FDA) yet, Brodsky said its being tested in late-stage clinical trials. He said there are already a number of other complement-inhibiting drugs in the pipeline for other diseases, including age-related macular degeneration, which may have a use in the fight against COVID-19.

There are a number of these drugs that will be FDA-approved and in clinical practice within the next two years, Brodsky said. Perhaps one or more of these could be teamed with vaccines to help control the spread of COVID-19 and avoid future viral pandemics.

The researchers findings were recently published in the journal Blood.

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COVID-19 immunity? Ottawa researchers to test long-term potency of coronavirus immune response – Global News

Saturday, October 17th, 2020

Researchers in Ottawa are embarking on a 10-month study to answer critical questions about how individual immune system responses to the novel coronavirus differ and how soon after infection a patient might be at risk again.

The teams findings could have major implications for vaccine research and help to predict an individuals risk of developing serious complications related to COVID-19, but one of the studys lead researchers warns the findings wont lead to any ironclad declarations of COVID immunity among recovered patients.

A team of researchers with the University of Ottawa and The Ottawa Hospital will study COVID-19 antibody and T cell responses from 1,000 subjects over the next 10 months. In an infection, T cells target infected cells and help to stimulate B cells, which then produce antibodies to neutralize pathogens and label them for disruption.

Half of the study participants will be people who have tested positive for the novel coronavirus, while the other half will be a surveillance cohort of front-line workers and other people who would have a high risk of exposure to the virus but might not have been tested for infection.

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The goal will be to test how long these subjects immune systems produce antibodies capable of neutralizing the pathogen after the initial infection.

Dr. Marc-Andr Langlois, professor with the University of Ottawas Faculty of Medicine, tells Global News the study idea was first proposed in the spring to answer an integral question in combating the novel coronavirus pandemic.

Since the very beginning of the epidemic, we were quite sure everyone who is infected will make antibodies, but how long will those antibodies last and how long will that protection last?

The question of COVID immunity has been in the spotlight in recent weeks, with U.S. President Donald Trump proclaiming to be immune to COVID-19 after testing positive and subsequently recovering from the virus.

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Health experts have said Trumps messaging, which has included assertions that others who tested positive for the coronavirus are also immune, are extremely dangerous. Recent examples of individuals twice testing positive for the virus are also throwing those claims into doubt.

Langlois says Trump is a complicated case because of the experimental treatment he was given, which saw him treated with external antibodies rather than just developing them on his own.

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Typically, an infected individuals immune response will develop its own antibodies and T cells the immune systems one-two punch to combat the pathogen. T cells and B cells can then form a memory of sorts that recognizes familiar pathogens and triggers a stronger response the next time a similar virus enters the immune system.

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The basis of long-term immunity is having these sentinels that remain in your lymph nodes and your bone marrow so that if youre re-exposed to the pathogen, you will be able to produce a fresh lot of antibodies on your own. These will be produced by your own cells and these will protect you, Langlois explains.

In the case of Trump, those antibodies came from an outside source and neutralized the virus. It is unknown if he has any memory B cells or memory T cells, he says.

But even in a typical immune response scenario, which can include an internal response triggered by an external vaccine, memory cells tend to fade after a period of time.

Because of the natural waning immunity to these antigens, vaccinations often require booster shots to restimulate the immune response for the long-term.

One of the most integral takeaways from the upcoming research, then, will be establishing the window of time when a booster would be needed for anyone receiving the upcoming COVID-19 vaccines so that the immunization sticks.

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The convalescent cohort those who have had lab-confirmed cases of the novel coronavirus will be monitored over the next 10 months for their levels of neutralizing antibodies to help determine when the post-recovery immunity typically fades.

The other 500 participants who were at high risk of exposure but did not get a positive test will be tracked for their own immune responses.

Researchers are betting that a portion of the group, maybe five to 10 per cent, might have been infected early on in the pandemic and shown no or mild symptoms, making their immune responses especially important for determining what gives an individual more effective protection against the virus.

Well be able to monitor and study how these immune system responses are different from person to person and try to find predictors of disease severity, Langlois says.

By analyzing blood samples for neutralizing antibodies from these two cohorts, Langlois says the studys findings could help determine a minimum threshold of protection that could then predict whether someones immune system is likely to keep them safe from infection or more serious complications related to COVID-19.

He cautions, however, that immune responses vary greatly from person to person, and that the study wont give a standardized timeframe of immunity after a coronavirus infection. At best, the study could provide probabilities of infection based on various individual predictors, such as genetic markers.

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Well never know for sure if they can get reinfected or what the severity of that infection is, Langlois says.

It will never be a black and white scenario where we say, Heres your stamp youre protected.

The Ottawa-based team, which includes epidemiologists, clinicians, legal and ethics experts, hopes to publish findings from the study in a years time, but Langlois notes that some research updates will likely be published as they go, given the time-sensitive nature of the work.

The researchers are currently looking for more participants in their study.

2020 Global News, a division of Corus Entertainment Inc.

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Coronavirus reinfection cases: what we know so far and the vital missing clues – The Conversation UK

Saturday, October 17th, 2020

As President Trump claims that he is immune to COVID-19 and isolated reports emerge of reinfection, what is the truth about immunity to COVID-19?

To date, there have been six published cases of COVID-19 reinfection, with various other unverified accounts from around the world. Although this is a comparably small fraction of the millions of people known to have been infected, should we be concerned? To unpick this puzzle, we must first consider what we mean by immunity.

When we are infected with any pathogen, our immune system quickly responds to try to contain the threat and minimise any damage. Our first line of defence is from immune cells, known as innate cells. These cells are not usually enough to eliminate a threat, which is where having a more flexible adaptive immune response comes into play our lymphocytes.

Lymphocytes come in two main varieties: B lymphocytes, which make antibodies, and T lymphocytes, which include cells that directly kill the germy invaders.

As antibodies are readily measured in blood, they are often used to indicate a good adaptive immune response. However, over time, antibodies levels in our blood wane, but this doesnt necessarily mean protection is lost. We retain some lymphocytes that know how to deal with the threat our memory cells. Memory cells are remarkably long-lived, patrolling our body, ready to spring into action when needed.

Vaccines work by creating memory cells without the risk of a potentially fatal infection. In an ideal world, it would be relatively easy to create immunity, but its not always that straightforward.

Although our immune system has evolved to deal with a huge variety of pathogens, these germs have also evolved to hide from the immune system. This arms race means that some pathogens such as malaria or HIV are very tricky to deal with.

Infections that have spilled over from animals - zoonotic diseases - are also challenging for our immune system because they can be completely novel. The virus that causes COVID-19 is such a zoonotic disease, originating in bats.

COVID-19 is caused by a betacoronavirus. Several betacoronaviruses are already common in the human population most familiar as a cause of the common cold. Immunity to these cold-causing viruses isnt that robust but immunity to the more serious conditions, Mers and Sars, is more durable.

Data to date on COVID-19 shows that antibodies can be detected three months after infection, although, as with Sars and Mers, antibodies gradually decrease over time.

Of course, antibody levels are not the only indication of immunity and dont tell us about T lymphocytes or our memory cells. The virus causing COVID-19 is structurally similar to Sars, so perhaps we can be more optimistic about a more durable protective response time will tell. So how worried then should we be about reports of reinfection with COVID-19?

The handful of case reports on reinfection with COVID-19 dont necessarily mean that immunity is not occurring. Issues with testing could account for some reports because virus can be detected after infection and recovery. The tests look for viral RNA (the viruss genetic material), and viral RNA that cannot cause infection can be shed from the body even after the person has recovered.

Conversely, false-negative results happen when the sample used in testing contains insufficient viral material to be detected for example, because the virus is at a very low level in the body. Such apparent negative results may account for cases in which the interval between the first and second infection is short. It is hugely important, therefore, to use additional measures, such as viral sequencing and immune indicators.

Reinfection, even in immunity, can happen, but usually this would be mild or asymptomatic because the immune response protects against the worst effects. Consistent with this is that most verified cases of reinfection reported either no or mild symptoms. However, one of the latest verified cases of reinfection which happened just 48 days after the initial infection actually had a more severe response to reinfection.

What might account for the worse symptoms the second time round? One possibility is the patient did not mount a robust adaptive immune response first time round and that their initial infection was largely contained by the innate immune response (the first line of defence). One way to monitor this would be to assess the antibody response as the type of antibody detected can tell us something about the timing of infection. But unfortunately, antibody results were not analysed in the recent patients first infection.

Another explanation is that different viral strains caused the infections with a subsequent impact on immunity. Genetic sequencing did show differences in viral strains, but it isnt known if this equated to altered immune recognition. Many viruses share structural features, enabling immune responses to one virus to protect against a similar virus. This has been suggested to account for the lack of symptoms in young children who frequently get colds caused by betacoronaviruses.

However, a recent study, yet to be peer-reviewed, found that protection against cold-causing coronaviruses did not protect against COVID-19. In fact, antibodies recognising similar viruses can be dangerous accounting for the rare phenomenon of antibody-dependent enhancement of disease (ADE). ADE occurs when antibodies enhance viral infection of cells with potentially life-threatening consequences.

It should be emphasised, though, that antibodies are only one indicator of immunity and we have no data on either T lymphocytes or memory cells in these cases. What these cases emphasise is a need to standardised approaches in order to capture the critical information for robust evaluation of the threat of reinfection.

We are still learning about the immune response to COVID-19, and every piece of new data is helping us unpick the puzzle of this challenging virus. Our immune system is a powerful ally in the fight against infection, and only by unlocking it can we ultimately hope to defeat COVID-19.

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Coronavirus reinfection cases: what we know so far and the vital missing clues - The Conversation UK

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World food day: Healthy food habits to armor our immune system in the changing weather – The Financial Express

Saturday, October 17th, 2020

Key soldiers in the fight include vitamins like A, C, E, B6, D, and minerals like zinc, iron, and selenium that help maintain a strong immune system and they are also antioxidants. (Representational image: IE)

By Namit Tyagi

The Autumn season has just begun in the country and we all are starting to fall a little sick with the common symptoms of cold and cough. Most grown-ups face such common symptoms twice a year whereas in children it is observed to be around 5-6 times. Everytime the weather changes, the count of allergens in the air also spikes up to nearly 200 viruses. The most common virus is Human Rhinovirus (HRV) that causes 40% of all colds. Thus these are mild viruses and can be eliminated easily from our body by following few precautionary measures.

To keep your immune system strong this season, adapt certain dietary habits and enjoy the festive season without any hurdle:

Eat more citrus fruits and vegetables Citrus fruits are an amazing source of Vitamin-C. It strengthens our immunity system and keeps our skin smooth and elastic. Citrus fruits are also rich in Vitamin-B nutrients, copper, phosphorus, potassium and magnesium as well. For their antioxidants properties, add them in their mid-morning or evening snack in the form of either salad or juice. Infact, having an orange a day is sufficient enough to fulfill all our Vitamin-C requirements.

Make sure you eat enough protein Protein helps our body in infinite ways. From muscular development to improving digestion. It is an important compound required in blood oxygenation which is then carried in all over the body. Add protein in your every meal in an adequate amount to fulfill your protein requirements thus help your body produce antibodies to boost immunity. The sources of protein include lentils, egg whites, quinoa,soya, broccoli and other dairy & poultry products.

Dont overlook prebiotic foods Add prebiotic sources in your meal or smoothies. Prebiotics are found in foods such as onion, garlic, banana, and curd. They assist in maintaining a balanced gut microbiome, which is a vital player in how your immune system functions. Prebiotics work by increasing the population of good bacteria in the gut which in turn sparks the production of anti-inflammatory cytokines, which are tiny proteins that help the immune system function.

Get enough vitamins through your diet Key soldiers in the fight include vitamins like A, C, E, B6, D, and minerals like zinc, iron, and selenium that help maintain a strong immune system and they are also antioxidants. Some foods that are rich in these vitamins include carrots, sweet potatoes, bell peppers, strawberries, almonds, avocados, salmon, oysters, tuna, and lean chicken breast. Enjoy adding them to your regular meals, evening or morning salads and smoothies.

Add Herbs and spices in your diet Turmeric, black pepper, cinnamon, clove, Tulsi, Giloy, ashwagandha, Mulethi are ayurvedically known for boosting immunity, you can enjoy them as kadha or tea in the early morning or evening. You can add ashwagandha powder or tablet with milk at night or post-dinner to have sound sleep because sound sleep helps in boosting your immune health.

Thus, adding on a few basic ingredients from our kitchen in our dietary routine and swapping junk evening snacks with a bowl of fruits and sprouts could make a big difference in terms of health and energy levels in our body.

(The author is Co-Founder & Head Nutritionist, Neuherbs & Neusafe India. Views expressed are personal.)

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World food day: Healthy food habits to armor our immune system in the changing weather - The Financial Express

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