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Scientists have discovered antibodies that react to the new coronavirus in blood samples donated prior to the start of the pandemic. They suggest that some people may have at least a degree of preexisting immunity to the new virus.

The number of new COVID-19 cases is on the rise in many regions across the globe. But not everyone who comes into contact with SARS-CoV-2, the new coronavirus, develops COVID-19.

A group of scientists from the Francis Crick Institute, in London, along with colleagues at University College London, both in the United Kingdom, may have found a clue as to why some people can fight off a SARS-CoV-2 infection better than others.

Their work recently appeared in the journal Science.

Surprise discovery

The research team originally set out to develop a high-sensitivity test to detect antibodies to the SARS-CoV-2 virus.

Scientists can use this type of test to establish whether a person has antibodies after they had COVID-19, which is a key piece of information for those trying to establish how long immunity may last after SARS-CoV-2 infection.

As part of their work, the scientists used serum samples provided by people who did not have COVID-19. To their surprise, they found antibodies that reacted to SARS-CoV-2 in some of the samples.

In their paper, the researchers describe a scientific theory that exposure to any of the common human coronaviruses, which can cause the common cold, may lead to immunity against the other common human coronaviruses. They refer to this as immune cross-reactivity.

There are four seasonal common human coronaviruses, all of which mostly cause mild disease. The vast majority of people have an infection with at least one of these viruses at some point.

Scientists already know that our bodies do not build up long-lasting immunity to these viruses, which is why a person can contract an infection with a common human coronavirus more than once in their lifetime.

But can a previous exposure to a common human coronavirus provide at least temporary protection against SARS-CoV-2?

Finding cross-reacting antibodies

Coronaviruses use a protein called the spike protein to attach to and infect host cells.

Prof. George Kassiotis, a senior author of the new study and the group leader of the Retroviral Immunology Laboratory at the Francis Crick Institute, explains how antibodies that recognize a part of the spike protein may provide immune cross-reactivity.

“The spike of this coronavirus is made of two parts, or subunits, performing different jobs. The S1 subunit allows the virus to latch onto cells and is relatively diverse among coronaviruses, whereas the S2 subunit lets the virus into cells and is more similar among these viruses,” he says. “Our work shows that the S2 subunit is sufficiently similar between common cold coronaviruses and SARS-CoV-2 for some antibodies to work against both.”

In their study, Prof. Kassiotis and colleagues determined the levels of cross-reacting antibodies in several collections of samples, most of which had been donated prior to the emergence of the SARS-CoV-2 virus.

In a group of 50 blood samples from pregnant people from May 2018, the team found that 10% had cross-reacting antibodies. In a separate cohort of 101 samples from May 2019, three had these antibodies.

In a further experiment, the team analyzed 13 additional samples from adults who had recently had an infection with a common cold coronavirus. Of these, only 1 sample had cross-reacting antibodies.

Overall, the authors report, 16 of 302 samples, or 5.29%, had SARS-CoV-2 cross-reacting antibodies. The median age of the donors was 51 years.

But why did relatively few people have cross-reacting antibodies, given that infections with common human coronaviruses happen frequently?

“This suggested that their emergence was not simply a common transient event following each [common human coronavirus] infection in this age group,” the authors comment. “Instead, given that [common human coronavirus]-reactive antibodies are present in virtually all adults, the rarity of SARS-CoV-2’s cross-reactivity […] indicates additional requirements.”

One such requirement, they suggest, may involve how often a person has an infection with a common human coronavirus. The frequency is highest in children and adolescents.

Children ‘more regularly exposed to other coronaviruses’ 

To look for a link between age and SARS-CoV-2 cross-reacting antibodies, the team analyzed 48 blood samples from children and adolescents aged 1–16 years. All of the samples stemmed from before the pandemic.

Here, they found that 21 of the samples had cross-reacting antibodies, while in a separate cohort of samples from people aged 17–25 years, these were only present in one sample.

“Our results show that children are much more likely to have these cross-reactive antibodies than adults. More research is needed to understand why this is, but it could be down to children being more regularly exposed to other coronaviruses,” comments Kevin Ng, one of the lead study authors and a post-graduate student in Prof. Kassiotis’ lab.

“These higher levels we observed in children could also help explain why they are less likely to become severely ill with COVID-19. There is no evidence yet, however, that these antibodies prevent SARS-CoV-2 infection or spread.” – co-lead study author Kevin Ng

Professor Kassiotis also weighs in: “It is important to stress that there are still many unknowns which require further research. For example, exactly how is immunity to one coronavirus modified by exposure to another?”

“Or, why does this activity decline with age? It is not the case that people who have recently had a cold should think they are immune to COVID-19,” he adds.

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A recent study reveals that losing fat without reducing muscle mass results in a significantly lower risk of heart failure in people with type 2 diabetes.

In the United States, around 1 in 10 people have diabetes, and 90–95% of them have type 2 diabetes. Type 2 diabetes usually develops after age 45. Estimates suggest that by 2045, 700 million adults worldwide will have this condition.

Type 2 diabetes usually begins as insulin resistance. This is a condition wherein the body’s cells no longer react to the insulin the pancreas produces to control blood sugar.

Genetics, ethnicity, and advancing age all play a role in the development of insulin resistance and diabetes. However, excess weight, a lack of exercise, an unhealthful diet, and smoking may be driving factors in its occurrence.

Once doctors diagnose this condition, the primary treatments they advise generally include taking medications and making certain lifestyle changes, such as losing weight and improving the diet.

As diabetes nearly doubles the risk of death due to heart disease or stroke and increases the risk of having heart failure by a factor of two in males and five in females, many researchers are focusing on preventing these and similar health complications for those with diabetes.

Heart failure, or congestive heart failure, occurs when the heart muscle does not pump the blood adequately. This leads to a buildup of fluid in the lungs or legs, or sometimes both.

Heart failure has a number of potential causes. For example, after a heart attack (when the heart muscle sustains damage due to a lack of oxygen), the muscle is weak and cannot pump well.

Heart failure can also occur due to type 2 diabetes. This is as a result of direct harm to the heart muscle from raised blood sugar and systemic inflammation associated with the condition.

One prevention strategy includes weight loss for people with overweight or obesity. However, not much is known regarding what type of weight loss has the most impact on reducing the risk of diabetes-related heart issues.

The study

To investigate this further, researchers at the University of Texas Southwestern Medical Center (UTSW) in Dallas analyzed data from the Look AHEAD study.

This is a randomized trial investigating weight loss due to intensive lifestyle intervention, consisting of healthful eating and increased physical activity versus support and education alone in people with type 2 diabetes.

The UTSW research, which appears in the journal Circulation, received funding from the National Heart, Lung, and Blood Institute, the Texas Health Resources Clinical Scholars Program, and the National Institutes of Health (NIH).

The researchers selected 5,103 people from the Look AHEAD study who did not have heart failure at the beginning of the study. The participants also had sufficient baseline measurements needed for prediction equations to estimate how much fat mass and lean (muscle) mass they had.

Data on the participants’ weight and waist circumference were available at the beginning of the study and over a 4-year period. The team also noted hospitalizations for heart failure over a 12-year time frame.

During the trial’s 12-year follow-up, 257 study participants were hospitalized for heart failure treatment.

In the Look AHEAD study, scientists used a scanning technique called dual-energy X-ray absorptiometry (DXA) to determine body composition in a subset of about 1 in 5 of the participants. These participants also had information recorded on factors such as height, weight, waist circumference, and ethnicity.

This meant that the researchers could validate existing equations that predict the proportion of fat mass and lean mass from these factors, which are simple to collect compared with the much more complicated process of conducting a DXA scan.

The researchers’ analysis of the subset of participants with DXA scans provided a new equation specific to this study group. They applied this new equation to the remaining participants without a DXA scan to accurately predict their fat mass and lean mass.

This revealed that adults in the study who had lost weight were less likely to develop heart failure if they lowered their fat mass and waist circumference. However, losing lean mass did not change their risk.

The investigators note that although the risk of heart failure decreased in those who lost body fat and reduced their waist circumference, the study data showed no significant reductions in heart attack risk.

The team also considered the participants’ ejection fraction (EF) ratio. This is a measurement of the amount of blood leaving the heart with each contraction.

The data showed that reducing body fat mass by 10% resulted in a 22% lower risk of heart failure with preserved EF ratio and a 24% lower risk of heart failure with reduced EF ratio.

“Our study suggests that simply losing weight is not enough. We may need to prioritize fat loss to truly reduce the risk of heart failure.” – Study co-author Dr. Kershaw Patel, a cardiologist at Houston Methodist Hospital in Texas

Supporting evidence

A study from May this year, which appears in the journal Circulation Research, compared obesity phenotypes, diabetes, and cardiovascular diseases.

The comparison suggests that some people who have a healthy weight or overweight but an excess amount of fat deposits around the internal organs and under the skin have a higher risk of diabetes and heart disease.

The researchers say that it is not possible to determine the risk of cardiovascular disease and type 2 diabetes based on body mass index (BMI) alone — mostly because body composition is so diverse.

They suggest that since excessive amounts of fat tissue largely define cardiovascular risks, reducing body fat is critical for prevention.

Implications and limitations

The results of the UTSW study suggest that for people with diabetes who also have overweight, losing weight, in general, may not be adequate to reduce heart health risks.

If further studies replicate these findings, it could confirm that losing weight by shedding visceral fat from around the organs — rather than losing muscle mass — is a key factor when it comes to reducing the risk of heart failure in type 2 diabetes.

The study authors also say that further investigation is necessary to determine if building or maintaining muscle in addition to losing fat mass would be even more effective in reducing the risk of diabetes-related heart failure.

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In a small clinical trial, patients with major depressive disorder (MDD) who were given two doses of psilocybin along with psychotherapy showed a reduction in depressive symptoms. The psychedelic’s therapeutic effects persisted for up to 4 weeks with minimal side effects.

Psychedelics are known for their hallucinogenic properties, but their mind-altering effects may also benefit people with depression.

According to the National Institute of Mental Health, about 17.3 million adults in the United States have experienced at least one depressive episode.

Currently, the gold standard for treating MDD is psychotherapy or antidepressant medication. A 2014 study in World Psychiatry found that psychotherapy combined with antidepressants was more effective than the former alone.

Replacing antidepressants with hallucinogenic mushrooms

New antidepressants are ketamine-like drugs that show a high therapeutic response. A 2014 meta-analysis in Psychopharmacology reports that roughly 0.5 milligrams per kilogram of ketamine effectively reduced depressive symptoms. These effects also lasted 2–3 days after treatment. However, there are some drawbacks.

While currently approved by the Food and Drug Administration (FDA), there are some short-term side effects to consider when using ketamine, such as feeling strange or bizarre, numbness, and difficulties speaking.

Ketamine has a high liability for addiction and may have a large potential for abuse. A 2018 study in Neurobiology of Stress found that repeated low-dose ketamine treatments for treatment-resistant depression resulted in cognitive impairments and potential for abuse.

To avoid people abusing their medication, alternative treatments to support psychotherapy are needed — enter psilocybin.

There is growing evidence of psilocybin’s antidepressant properties. A study in the Journal of Psychopharmacology demonstrateda single psilocybin dose that produced an antidepressant and anxiolytic response in cancer patients, which lasted for 5 years.

Compared with ketamine, psilocybin has lower addictive properties, which would be beneficial as a potential add-on for current treatments. However, clinical research evaluating this substance in combination therapies is limited.

Recently, researchers at Johns Hopkins University published an article contributing to the research investigating the effectiveness of psilocybin-assisted therapy for depression.

“These data expand the findings of previous studies involving patients with cancer and depression, as well as patients with treatment-resistant depression, by suggesting that psilocybin may be effective in the much larger population of MDD,” write the study authors.

Their clinical trial results appear in JAMA Psychiatry.

Johns Hopkins clinical trial

From August 2017 to April 2019, the researchers of the current study recruited adults with MDD who were not taking antidepressant medications and had no history of psychotic disorder, suicide attempts, or hospitalizations. The scientists randomly assigned a total of 24 participants to an immediate or a delayed treatment group.

The psychedelic-assisted therapy lasted for 8 weeks, with 18 in-person visits and 2 days for psilocybin treatment.

Participants in the immediate treatment group began the psilocybin treatment during an 11-hour supportive psychotherapy session. The researchers allowed for a 1.6-week break between the first and second doses. In contrast, the delayed treatment group waited 8 weeks before receiving psilocybin-assisted therapy.

Reduction in severity of depression

At the time of enrollment, participants had a score of 23 in the GRID-Hamilton Depression Rating Scale (GRID-HAMD), which indicates moderate depression. After a 1-week and 1-month follow-up, participants in the immediate treatment group dropped to a score of 8, indicating mild depression.

In the entire cohort, 67% reduced the severity of their depressive symptoms 1 week after psilocybin treatment. This percentage grew to 71% when researchers followed up after 4 weeks.

After 1 week, the researchers found that 58% of the cohort were no longer classified as clinically depressed. By week 4, they found that 54% of the participants were no longer classified as depressed.

Limitations from the clinical trial design

Several limitations exist that could challenge the usefulness of the study results. The research had insufficient minority representation, as recruitment leaned towards non-Hispanic whites.

This is important because while white people typically report more cases, the American Psychiatric Association note that Black and Hispanic Americans are more likely to experience depression for more extended periods. In response, the researchers acknowledge the need for future studies to validate this proof of concept in more representative populations.

The study also fails to address the long-term effects of psilocybin treatment. Unlike the investigation on cancer patients, which had a 5-year follow up, the current research followed up after only 1 month.

There were also variables in the study design that could question psilocybin’s effectiveness as an antidepressant drug. One comes from a lack of a placebo group. Placebos are essential in determining whether a person truly benefitted from the drug and not from outside factors. For this reason, the safety of using psilocybin remains unknown.

Final thoughts

Overall, the authors find their clinical trial supports the use of psilocybin-assisted therapy for MDD.

“Although the rapid antidepressant effects of psilocybin are similar to those reported with ketamine, the therapeutic effects are different. Ketamine effects typically last for a few days to 2 weeks, whereas the current study showed that clinically significant antidepressant response to psilocybin therapy persisted for at least 4 weeks, with 71% of the participants continuing to show a clinically significant response (≥50% reduction in GRID-HAMD score) at week 4 of follow-up.”

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A study finds that social anxiety and depression lead to a greater use of dating apps and affect what people hope to gain from them.

Pew Research Center data released in February this year indicate that, in the United States, as many as 30% of adults have used a dating site or app.

According to a Statista survey, in the first quarter of 2020, Tinder, the most popular of these apps, had more than 6 million subscribers.

There are numerous reasons for using a dating app. Now, a new study from Ryerson University in Toronto, Canada, looks specifically at the link between social anxietydepression, and dating apps.

According to this research, there is a link between social anxiety and depression and a more extensive use of dating apps.

“With increased symptoms of social anxiety and depression, women may be even more likely to turn to technology for social connection, especially if alternative forms of social contact are reduced due to social avoidance.” – Senior author Martin Antony, from Ryerson University in Toronto, Canada

The study appears in Cyberpsychology, Behavior, and Social Networking.

Why do people use dating apps?

Previous research suggests there are six things people who use Tinder hope to attain. These “Tinder motives” are:

  • love
  • casual sex
  • ease of communication
  • self-worth validation
  • thrill of excitement
  • trendiness

The prevailing theory tested in the new research is the positive link between social anxiety and depression with a greater use of dating apps. In addition, the researchers predicted positive associations between social anxiety and depression and a desire for:

  • ease of communication for men, due to the anxiety associated with asking potential partners for a date, traditionally perceived as a male responsibility
  • love, equally for both genders
  • self-worth validation, equally for both genders
  • the thrill of excitement, especially for men
  • casual sex, especially for men

The study authors also predicted a negative association between social anxiety, depression, and contacting dating app matches equally for both genders.

The study’s findings

A total of 374 individuals who use dating apps were recruited for the study and responded to questions posed through Amazon’s Mechanical Turk platform.

There were no inclusion or exclusion criteria, and each person received $1 for taking part in the study.

The researchers asked participants to fill out the 17-question Social Phobia Inventory (SPIN), in which a person describes the anxiety they have experienced in social situations over the past week. Researchers recognize the SPIN survey for its usefulness as a psychometric measure.

In addition, individuals completed the equally well-regarded 21-question Depression Anxiety Stress Scales survey for measuring anxiety, depression symptoms, and stress.

Participants also completed the Tinder Motives Scale survey that tracked the importance of five of the six Tinder motives to the individual. The research team did not include trendiness because they considered the survey ineffective for measuring its significance.

The scientists measured individuals’ use of dating apps through the Online Dating Inventory questionnaire to assess their use and behavior.

The researchers found that social anxiety and depression are not interchangeable, and were variously linked, or not, with different motives for using dating apps.

The researchers’ general hypothesis was deemed correct: social anxiety and depression do appear to be associated with greater dating app use. Beyond that, the authors of the study drew a variety of conclusions.

They found that:

  • Social anxiety and depression are associated with the use of dating apps for ease of communication by both genders, though the effect is more pronounced for women.
  • Women with social anxiety are more likely to be interested in obtaining love through dating apps. Depression did not affect whether people were looking for this, for either men or women.
  • Dating apps are used for self-worth validation by people of both genders with social anxiety. This was also true of people with depression, with a stronger effect in women than men.
  • Contrary to the researchers’ expectations, there was a positive link between social anxiety and the thrill of excitement for women, though not for women living with depression, and not for men.
  • There was an association between social anxiety in men and women with an effort to obtain casual sex. This was also true in people living with depression, with a stronger effect in women.

The researchers also discovered a negative correlation between social anxiety and depression in men and the likelihood that they would actually contact a person who turned out to be a match. The likelihood a woman would initiate contact was not affected at all by their level of depression.

The study authors point out that they cannot know whether social anxiety and depression lead to greater dating app use or the other way around, suggesting this open question would benefit from further research.

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In our ‘Hope behind the headlines’ series, we continue to round up the most encouraging results in COVID-19 research. But, as the pandemic continues to unfold with many countries embracing a second lockdown, a critical approach to these hopeful results is more necessary than ever.

In a live social media chat, Dr. Anthony Fauci announced a few days ago that the first doses of a safe coronavirus vaccine are set to become available in late December this year or early January 2021. This is, of course, if everything continues to go smoothly.

Dr. Fauci, the director of the National Institute of Allergy and Infectious Diseases (NIAID), was referring to two candidate vaccines currently underway: one in development by Moderna Therapeutics in collaboration with NIAID, and the other in development by Pfizer in partnership with BioNTech.

Since then, Pfizer announced a 90% effectiveness rate for its candidate vaccine. In this article, we track the progress of these therapeutics and offer a critical — yet hopeful — perspective.

Why mRNA vaccines are speedier

MNT recently covered what Tal Zaks, Chief Medical Officer of Moderna Therapeutics, and Prof. Uğur Şahin, co-founder and CEO of BioNTech, had to say about their candidate vaccine at the recent Wired Health:Tech event.

Both the Moderna-NIAID and Pfizer-BioNTech vaccines use mRNA — that is, they use genetic information rather than a viral base to “train” the immune system to respond to SARS-CoV-2, the new coronavirus that causes COVID-19.

The speakers explained how an mRNA-based vaccine could be made available faster and is generally superior to other types of vaccines that use a viral base.

They cited “the infrastructure required” as being “relatively small and quick.” They also mentioned that, because the starting point is genetic information rather than the virus itself, “there is a component of speed that allows you to get into the clinic and then […] scale-up manufacturing.”

However, it is worth noting that while both of these candidate mRNA vaccines for COVID-19 show promise in early-stage clinical trials, there is no data available yet to confirm that they can prevent people from developing the disease.

It is also important to note that there are no human-licensed mRNA vaccines for other diseases. If the Food and Drug Administration (FDA) approve these vaccines, it will be groundbreaking, not just in the fight against COVID-19, but for mRNA vaccines in general.

By December we should know if we have a safe, effective vaccine

Both candidate vaccines are currently in stage 3 of clinical trials, to test their efficacy in large-scale studies comprising tens of thousands of people.

Moderna expects to release its trial stage results later in November. By December, we should know “whether or not we have a safe and effective vaccine,” Dr. Fauci said in the live session.

Pfizer announced the results of its late-stage clinical trials this week. In a move that boosted stock markets across the globe, the company said their candidate vaccine is 90% effective. Dr. Albert Bourla, Pfizer’s CEO, hailed the results as a “great day for humanity.”

“Today is a great day for science and humanity. The first set of results from our phase 3 COVID-19 vaccine trial provides the initial evidence of our vaccine’s ability to prevent COVID-19.” – Dr. Albert Bourla

However, it is worth noting that, at the time of publication, Pfizer have not yet released their data. It is likely their 90% effectiveness rate derives from a small number of participants. Therefore, questions remain about whether the candidate vaccine is safe and effective in older adults and vulnerable populations, who are likely to receive it first.

As soon as the data are released, MNT will cover the ins and outs of the trial and offer a critical perspective.

However, as Dr. Fauci said in his live session, if everything goes well, the first vaccine doses will become available to high-risk people and groups considered most vulnerable and most in need “by the end of December or the beginning of January.”

However, it is unlikely that life will return to normal “until the end of 2021 at least,” he continued. This is because it will take a while before a vaccine is mass-distributed, and even after it is, vaccine-induced immunity takes some time to build up on a national and then global level.

While the end of 2021 feels like a long while ahead, there are other reasons to keep our hopes up in the meantime. Here are other immunity-related scientific findings that we can add to our arsenal in the fight against the new coronavirus.

More proof of long-lasting immunity

Scientists have shown that those who have had the virus may have at least some level of lasting immunity. This is helpful not just for those who have had the infection, but also for using their plasma and possibly T cells to treat others.

For instance, researchers at the University of Arizona College of Medicine in Tucson have found that people who have had COVID-19 develop long-lasting immunity. Their study appears in the journal Immunity.

The Tucson scientists tested for SARS-CoV-2 antibodies in almost 6,000 people right after the infection and again several months later. Co-lead researcher Prof. Deepta Bhattacharya says, “We clearly see high-quality antibodies still being produced 5–7 months after SARS-CoV-2 infection.”

“Many concerns have been expressed about immunity against COVID-19 not lasting. We used this study to investigate that question and found immunity is stable for at least 5 months.” – Prof. Deepta Bhattacharya

The researcher is likely referring to a few studies that point to declining antibodies over time, such as the study conducted at Imperial College London in the United Kingdom. However, the results obtained by Prof. Bhattacharya’s team counter these findings.

Even more hopeful is the parallel that Prof. Bhattacharya draws with SARS-CoV-2’s cousin, SARS-CoV, where evidence suggests immunity could last 12–17 years.

“If SARS-CoV-2 is anything like the first one, we expect antibodies to last at least 2 years, and it would be unlikely for anything much shorter,” he says.

Over 90% of COVID-19 patients had antibodies for 5 months

Another study that appears in the journal Science also adds credence to this notion of long-lasting antibody immunity.

This large-scale analysis summed up over 30,000 people and found that most of those who had the virus and experienced mild-to-moderate disease “experience robust […] antibody responses” lasting up to 5 months.

Florian Krammer, Ph.D., from the Department of Microbiology at the Icahn School of Medicine at Mount Sinai, New York, NY, is the study’s senior author. He says:

“While some reports have come out saying antibodies to this virus go away quickly, we have found just the opposite — that more than 90% of people who were mildly or moderately ill produce an antibody response strong enough to neutralize the virus, and the response is maintained for many months.”

However, the scientists note that their study is not proof that these antibodies protect against reinfection. But, they say, it is also unlikely that they wouldn’t offer protection. More studies are needed to prove this with certainty.

“Although this cannot provide conclusive evidence that these antibody responses protect from reinfection, we believe it is very likely that they will decrease the odds ratio of reinfection, and may attenuate disease in the case of breakthrough infection.” – Florian Krammer et al.

“We believe it is imperative to swiftly perform studies to investigate and establish a correlation of protection from infection with SARS-CoV-2,” conclude Krammer and colleagues.

Antibodies from older males may be most helpful

These antibodies have the potential to protect people from severe cases of COVID-19, while some people’s antibodies may be stronger and more helpful than others.

A new study — led by Prof. Sabra Klein, of the Johns Hopkins Bloomberg School’s Department of Molecular Microbiology and Immunology in Baltimore, MD — tested the ability of antibody-rich blood plasma to inactivate the new coronavirus in cells containing the virus.

The researchers used widely available tests to determine the level of antibodies in 126 adults who had recovered from mild or moderate, lab-confirmed COVID-19. They wanted to see which donors provided the strongest antibodies.

The team found that a strong antibody response correlated with being hospitalized for the disease, being male, and being older.

“We propose that sex, age, and severity of disease should be used to guide the selection of donors for convalescent plasma transfer studies because we found that these were significant patient characteristics that not only predicted the amount of antibody but the quality of that antibody.” – Prof. Sabra Klein

T cells may succeed if antibodies fail

It is worth noting that some studies question the “lifespan” of antibodies, such as the recently published Imperial College London study. But even if antibodies may decline shortly after infection — a hypothesis that is still contentious — there are other aspects of immunity that may help protect against COVID-19, for example, T cells.

A new study that used cell cultures suggests that adoptive immunotherapy — a technique where specialists take the cells that target the virus from the blood of someone who has had the virus and inject them in people with compromised immunity — could protect those with weakened immunity from severe COVID-19.

Dr. Michael Keller, a pediatric immunology specialist who led the study, comments on his team’s findings, saying, “We found that many people who recover from COVID-19 have T cells that recognize and target viral proteins of SARS-CoV-2, giving them immunity from the virus because those T cells are primed to fight it.”

“This suggests that adoptive immunotherapy using convalescent T cells to target these regions of the virus may be an effective way to protect vulnerable people, especially those with compromised immune systems due to cancer therapy or transplantation.”

However, it is important to note that this study was preclinical, used cell cultures, and even in those cells, it did not directly test T cells’ ability to destroy the new coronavirus.

Instead, the researchers found that the T cells stimulated an immune response to a small segment of the new coronavirus — a part of its membrane. Namely, they released interferon, which is crucial in the response to SARS-CoV-2 infection. Most other vaccines target the virus’ spike protein, but targeting the membrane could provide a new avenue for vaccine development.

Furthermore, the number of participants used for the study was relatively small, while many of the donors only had mild COVID-19 symptoms. Finally, not every participant had a positive COVID-19 or antibody test.

In our next installment of Hope behind the headlines, we will take a closer look at the role of T cells in offering immunity, as well as tracking the progress of the Pfizer-BioNTech vaccine.

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A trial suggests that in patients who are no longer responding to metformin, taking a combination of two newer drugs is safe and yields clinical benefits for at least 2 years.

Insulin helps regulate the amount of glucose circulating in the blood. In type 2 diabetes, the body does not produce enough insulin, its cells no longer respond effectively to the hormone, or both.

In the long term, high blood glucose levels can cause a wide range of debilitating and potentially life threatening complications. These include high blood pressure, damage to organs such as the heart and kidneys, nerve damage, and blindness.

According to the Centers for Disease Control and Prevention (CDC), type 2 diabetes affects more than 30 million individuals in the United States and accounts for 90–95% of all cases of diabetes.

Type 2 diabetes used to be called adult-onset diabetes because it mostly affects people over the age of 45. But in recent decades, rates of type 2 diabetes in children, teenagers, and young adults have increased in the U.S.

Lifestyle changes can control or even reverse the condition. Doctors also prescribe drugs to stabilize patients’ blood glucose levels.

The first-line treatment is metformin, but in some patients, the drug’s efficacy can decline over time, necessitating alternative treatments.

Drug combination

A clinical trial called DURATION-8 investigated a combination of two newer drugs — exenatide and dapagliflozin — in patients whose blood glucose levels did not respond to metformin.

Initially, the trial lasted 28 weeks, but it was later extended to 52 weeks. The results suggest that the combination was safe and continued to be more effective than either drug alone.

In addition to stabilizing blood glucose levels, the drug combination was associated with lower blood pressure and body weight.

The researchers report in the journal Diabetes Care that the drug duo remained safe and effective 2 years (104 weeks) after treatment began, following a second extension of the trial.

“Many therapies in diabetes management are short-lived, which is why it is useful to test for long-term effect,” says first author Dr. Serge Jabbour, director of the division of endocrinology and the Diabetes Center at Thomas Jefferson University in Philadelphia, PA.

Exenatide belongs to a class of drugs called glucagon-like peptide-1 receptor agonists, which work by promoting insulin secretion, reducing the release of glucose from the liver, and increasing the feeling of fullness after a meal.

Dapagliflozin belongs to a class called sodium-glucose cotransporter-2 inhibitors, which boost the amount of glucose that is excreted in urine.

“These two classes work synergistically to help control a type 2 diabetes patient’s glucose levels and other measures associated with diabetes,” says Dr. Jabbour. “We can now feel more confident about prescribing these medications long term.”

AstraZeneca, which makes branded versions of both drugs, funded the study. The company also played a role in designing the study, gathering the data, and evaluating it.

Study design

The researchers randomly assigned 695 adults with type 2 diabetes whose blood glucose was not adequately controlled by metformin to three treatment groups:

  • a weekly injection of exenatide and a daily oral dose of dapagliflozin
  • weekly exenatide and daily oral placebo
  • a weekly placebo injection and daily oral dapagliflozin

After 2 years, 431 patients remained in the trial. Most of the participants who dropped out did so because they did not want to sign up to an extension of the trial.

After adjustments for other possible contributing factors, those who received both drugs saw the greatest average reduction in their glycated hemoglobin (HbA1c) levels — a measure of the stability of blood glucose levels — compared with the start of the trial.

In patients who took both drugs, there were also improvements in blood glucose levels after fasting and 2 hours after eating, and reductions in body weight and systolic blood pressure.

The researchers report that patients tolerated well the combination of exenatide and dapagliflozin.

While patients experienced no episodes of major hypoglycemia (dangerously low levels of blood glucose), there were more episodes of minor hypoglycemia in patients who took both drugs compared with the other two experimental groups.

Conclusions

The authors conclude that the clinical benefits of taking both drugs were maintained for 2 years, with “no unexpected safety findings.” They continue:

“Further studies are needed to investigate whether the combination treatment effects observed in DURATION-8 could potentially extend to a reduced incidence of [cardiovascular] and renal events in patients with type 2 diabetes.”

The authors acknowledge that the relatively high proportion of patients who withdrew from the study after 1 year limits the “robustness” of its findings after 2 years.

Finally, they note that their findings may not apply to all patients. Treatment should be tailored to individuals and modified according to how well they progress.

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A new study has highlighted the prevalence of gastrointestinal symptoms in people with COVID-19 and what signs abdominal radiologists should look out for.

In a new study, researchers have synthesized evidence from 36 scientific articles to highlight the prevalence of gastrointestinal symptoms in people with COVID-19.

The study, appearing in the journal Abdominal Radiology, also identifies some of the signs abdominal radiologists should look out for when imaging people.

COVID-19 unknowns

One of the challenges of the COVID-19 pandemic has been the fact that SARS-CoV-2 is a novel coronavirus. While sharing some similarities with the previous severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 also has many differences.

As time progresses, scientists can conduct research on the virus to discover some of these unknowns and therefore help inform effective policy decisions and clinical practices. This has been the case with the symptoms of COVID-19.

While scientists have been aware of the most common symptoms — fever, coughing, loss of smell or taste, and shortness of breath — for some time, they have only recently identified other less common but significant symptoms.

As Dr. Mitch Wilson, a radiologist and clinical lecturer at the University of Alberta’s Faculty of Medicine & Dentistry and co-author of the study points out, “[t]here’s a growing amount of literature showing that abdominal symptomatology is a common presentation for COVID-19.”

The study

In the present article, a team of researchers focused on the growing evidence of people presenting with gastrointestinal issues linked to COVID-19.

To do this, the researchers conducted a study to highlight trends, issues, or areas that require more research.

The team searched through popular scientific databases using variations of the keywords “COVID-19,” “gastrointestinal,” and “imaging.” This resulted in 614 potentially relevant articles. The team identified a further 21 articles from other sources.

The researchers then removed duplicate articles and began screening the articles’ abstracts and titles for relevance, identifying 137 articles.

The researchers then conducted a full-text screening, limiting the studies to those that included findings related to abdominal imaging in people who had received a diagnosis of COVID-19.

The team included 36 articles in their study.

Gastrointestinal COVID-19 signs

After synthesizing the evidence from these 36 studies, the researchers identified two key findings.

First, gastrointestinal symptoms are a significant aspect of COVID-19 and may be present in the absence of other more well-known symptoms.

The researchers highlighted a meta-analysis covering more than 4,200 people that found 17.6% had gastrointestinal symptoms. In another study of 1,141 people, 16% presented with only gastrointestinal symptoms.

Second, the researchers identified a series of signs that an abdominal radiologist should look out for when imaging people — particularly because doctors have reported the incidental identification of COVID-19 in a substantial proportion of individuals with gastrointestinal symptoms.

The signs that the researchers suggest abdominal radiologists should look out for include:

  • bowel inflammation,
  • air within the bowel wall,
  • bowel perforation.

However, these signs are relatively rare in people with COVID-19. As Dr. Wilson points out, “[s]eeing these things is not necessarily telling us a patient has COVID-19. It could be from a variety of potential causes.”

“But one of those potential causes is infection from the virus, and in an environment where COVID-19 is very prevalent, it’s something to consider and potentially raise as a possibility to the referring physician.”

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With 47 COVID-19 vaccine candidates in testing, it is no wonder that there are myths and misconceptions about when a vaccine will actually be available to the public, and how safe it will be. Pan American Health Organization (PAHO) experts have recently addressed the media to clarify some of these issues.

The latest data from the World Health Organization (WHO) indicate that, as of November 3, 2020, there are 47 COVID-19 vaccine candidates in clinical trial phases around the world. There are also as many as 155 in preclinical testing.

Given the sheer number of vaccine candidates that researchers have developed within months of the start of the pandemic, it is only natural that questions and doubts have arisen about this process.

Traditionally, it can take years for a vaccine candidate to undergo testing for safety and efficacy and to gain official approval for distribution to the public.

However, scientists have been ramping up their efforts with the aim of bringing a COVID-19 vaccine to the public in record time.

At this year’s WIRED Health:Tech conference, Prof. Uğur Şahin, the co-developer of one of the most promising vaccine candidates so far — the “Pfizer vaccine” — explained that speeding up does not mean that scientists are rushing the process.

Rather, researchers have been optimizing the vaccine development process by sharing more data across research teams and conducting some of the tests in parallel, rather than consecutively, Prof. Şahin explained.

Still, many people continue to have questions and doubts regarding the safety and efficacy of future COVID-19 vaccines, as well as the development process for vaccine candidates.

To address some of these questions, specialists affiliated with or collaborating with the PAHO held a dedicated webinar on October 23, 2020.

The speakers included:

  • Dr. Cuahtémoc Ruiz-Matuz, chief of the Comprehensive Family Immunization unit at the PAHO
  • Dr. Jarbas Barbosa, PAHO assistant director
  • Dr. Alba María Ropero Álvarez, PAHO regional advisor on immunization
  • Dr. Lucia Helena de Oliveira, PAHO regional advisor on new vaccines

The context of immunization

During the webinar, Dr. Ruiz-Matuz suggested that the issues regarding an upcoming COVID-19 vaccine did not emerge in a vacuum.

For decades, healthcare policymakers have striven to make immunization against common pathogens available worldwide, particularly to prevent potentially dangerous childhood diseases.

Dr. Ruiz-Matuz spoke of the recent situation of worldwide immunization programs, noting that global coverage of vaccines for 1-year-olds is increasing, leading to a lower number of deaths due to preventable illness in infancy.

In the Americas, he said, cases of childhood diseases that countries have been vaccinating against over the past few decades have lowered drastically. This is the case with rubella, diphtheriapertussis, neonatal tetanus, and measles.

Some diseases, he added, have disappeared altogether — as is the case with polio and congenital rubella syndrome.

However, data from last year indicate that childhood immunization programs may be losing ground. “Of 25 children, three are completely left behind, while one starts the three-dose scheme and does not finish it,” Dr. Ruiz-Matuz pointed out.

Measles, mumps, and rubella vaccinations, in particular, have been on the decline in the past year. According to the PAHO specialist, “This is obviously the impact of the pandemic.”

Dr. Ruiz-Matuz also argued that, sometimes, the challenges that experts face at a local and global level when it comes to immunization are not intrinsic to health services.

Urbanization trends, natural disasters, local political contexts, the lack of social equity, the movement of populations between regions and countries, and country-wide financial crises are all added obstacles standing in the way of adequate vaccination.

Challenges for COVID-19 immunization

Dr. Barbosa noted that once a COVID-19 vaccine is finally available to the public, there will still be many challenges when it comes to distributing it across different populations.

According to him, these challenges include:

  • “ensuring equitable, timely, and sufficient access to the vaccine”
  • “addressing technical and logistic aspects” regarding vaccine development and production
  • “defining the priority groups to receive the first vaccine doses”
  • “determining the appropriate number of doses for adequate protection”

Widespread misinformation may further affect people’s trust in the COVID-19 vaccine and prevent them from getting inoculated against the new coronavirus, Dr. Barbosa also warned.

Mistrust in vaccines could also render the population more vulnerable to other preventable diseases, such as pertussis or measles.

Dr. Barbosa urged media representatives to provide information to the public based on hard scientific evidence, and to present it in a very transparent way, in order to fight current trends of misinformation.

Fighting vaccine hesitancy

Dr. de Oliveira spoke of the dangers of vaccine hesitancy, which, she argued, it is possible to reduce by increasing the public’s understanding of what vaccines are and how they work.

“Vaccines prevent diseases that can be dangerous, or even deadly. They greatly reduce the risk of infection by working with the body’s natural defenses to safely develop immunity to disease,” she explained.

“A vaccine is a part of a germ that is exposed to your immune system in a safe way, so that [the immune system] can learn how to fight off that harmful pathogen and protect your body from it in the future when this pathogen enters [the] body.” – Dr. Lucia Helena de Oliveira

The expert went on to cite WHO data that indicate that vaccines prevented at least 10 million deaths in 2010–2015.

She also noted that many fears around vaccines originate from the belief that, in some cases, they may cause rather than prevent infection. This is not true, she emphasized — but to understand why it is not true, it is necessary to have a clear understanding of how vaccines work.

“Vaccines help develop immunity by imitating an infection,” explained Dr. de Oliveira. “Once the imitation infection goes away, the body is left with a supply memory, and this memory will be activated when the germ — the virus or the bacteria, for example — enters […] your body.”

The imitation infection the vaccine triggers may cause minor symptoms similar to those a person might experience during illness, such as a fever. This is normal, the expert noted. It is a sign that the body is working and learning how to fight the pathogen. This is not the illness itself.

However, following vaccination, “it takes a few weeks for the body to produce antibodies” that can identify and help fight the pathogen.

In the meantime, she cautioned, exposure to an active virus just before or just after vaccination may still lead to disease, given that the vaccine has not yet had a chance to do its work.

Developing a COVID-19 vaccine

Vaccine development “is [a] very large and complex [process], often lasting 10–15 years,” Dr. de Oliveira added.

So, what about the fast work on the COVID-19 vaccine? Will it mean that the end result will not be as safe and effective as other vaccines? Not so, said the PAHO expert.

“It doesn’t mean that the vaccine is not going to be safe and [effective], because there are a lot of protocols [at] this moment — protocols from WHO, protocols from FDA [the Food and Drug Administration], protocols from EMA [the European Medicines Agency] — that [have] established rules for this vaccine, which is going to be produced in a much shorter time.”– Dr. Lucia Helena de Oliveira

Finding a safe and effective COVID-19 vaccine will also be possible because many research teams around the globe are looking at both old and new vaccine platforms. These include:

  • vaccines using a live virus with reduced infectivity
  • vaccines using an inactivated virus
  • vaccines using genetic information
  • viral vector vaccines
  • protein-based vaccines

Moreover, for a vaccine to become licensed for public distribution, it has to successfully pass through three clinical trial phases, Dr. de Oliveira explained.

Phase 1 is a small-scale safety study, phase 2 is an extended safety trial in hundreds of volunteers, and phase 3 is a large-scale trial in thousands of volunteers.

Phase 3 trials test for safety, dosage, and efficacy, as well as possible side effects across various demographics, she noted.

If phase 3 trials are successful, national healthcare decision makers will likely approve the vaccine’s release to the public.

However, the work does not stop there. Dr. de Oliveira said that there is also a phase 4, during which experts distribute the vaccine through immunization programs and the researchers continue to monitor its safety and effectiveness.

Challenges when a vaccine is ready

There are some real challenges ahead once a vaccine is ready and declared safe and effective. The PAHO experts noted that people should not forget these challenges or take them lightly; rather, they should try to understand them for what they are.

Dr. Ropero Álvarez said that the current working scenario is that there will be limited doses of the COVID-19 vaccine available for distribution, meaning that decision makers will have to prioritize their distribution to specific groups.

The WHO co-lead COVAX, which is an international program wherein experts and institutions from 172 countries are collaborating to ensure that a safe, effective COVID-19 vaccine will be available to all.

Dr. Ropero Álvarez cites data that indicate that, to begin with, countries participating in the COVAX program will receive doses that will likely be enough to cover 20% of their population.

Around 3% of doses will likely go to health and social care workers, and around 17% will likely go to high risk adults, such as those with chronic conditions and older adults. It is also possible that some doses may go to additional high priority groups, depending on each country’s situation.

Participating countries will have to conduct very clear communication campaigns, explaining why these groups will take priority in COVID-19 immunization programs, the PAHO expert noted.

Asian female buying some wine at a supermarket

Doctors have warned that people in the United States may be drinking excessively as a way to cope with the COVID-19 pandemic.

In a new viewpoint article, two doctors have warned that more people in the U.S. may be turning to alcohol as a way of coping with the “myriad stressors” of the COVID-19 pandemic.

The article, published in the Journal of General Internal Medicine, proposes a series of interventions to try to minimize this behavior and better support people with alcohol use disorder.

Coping strategy

It is well documented that drinking alcohol is one way that people cope with stressful situations. For example, research has shown that in the U.S., people tend to drink more alcohol following terrorist attacks.

Furthermore, if a person has alcohol use disorder, they are more likely to use alcohol to cope with the stress of a traumatic event.

In this context, the current COVID-19 pandemic is a particular cause for concern. The authors of the current article point out that rather than being a single event, the effects of the COVID-19 pandemic are prolonged over time, potentially exposing people to ongoing trauma.

Further, the pandemic has caused various potential stressors that a person may cope with by drinking alcohol.

As well as the catastrophic effect on people’s health and the loss and grief experienced by many, the pandemic has also disrupted economies and social and cultural life, threatening people’s jobs, disrupting their interpersonal support structures, increasing barriers to health care, and forcing many people into isolation.

Before the pandemic, researchers had noted that people in the U.S. were tending to drink more. This was particularly the case for females.

Recent research suggests that people in the U.S. increased their alcohol consumption in the early phase of the pandemic. This is in line with similar findings from studies in the United Kingdom and Australia.

Alcohol health effects

This matters because well-documented links exist between increased alcohol consumption and adverse health outcomes.

As the National Institute on Alcohol Abuse and Alcoholism point out, alcohol consumption can change mood and behavior, damage a person’s heart, liver, and pancreas, increase the risk of several types of cancer, and weaken a person’s immune system.

Research has also linked excessive alcohol consumption to mental health disorders, such as anxiety and depression, which may worsen during the pandemic.

Consequently, it is important to encourage people to find alternative coping strategies in response to the stressors of the pandemic. Effective support should also be available for people experiencing the effects of increased alcohol consumption or people with alcohol use disorder.

Interventions

The authors of the present study offer various suggestions for interventions that may help reduce people’s dependence on alcohol during the pandemic. Other suggestions focus on better preparing clinical services to support people with substance abuse issues.

According to Dr. Shelly F. Greenfield, director of the Alcohol, Drug, and Addiction Clinical and Health Services Research Program at McLean Hospital in Belmont, MA, “[i]ncreasing identification of harmful alcohol use in patients and intervening early are key components of addressing this problem.”

“In addition, recognition of the problem from policymakers could lead to changes in federal regulations — such as we have seen with telehealth — and improvements in access to healthcare,” she notes.

The authors suggest that public health messaging should raise awareness of the potential for increased drinking during the pandemic, as well as giving advice on alternative coping strategies for the stressors of the pandemic.

They also suggest that primary care practitioners should offer increased screening for alcohol use disorder when people contact primary care services.

Technologies, such as telehealth — that enable clinical information to pass between doctors and individuals at a distance — may also be valuable for people who are isolating or where the pandemic has forced a reduction in the enrolment for some face-to-face clinical services.

Finally, the authors highlight that ensuring people have access to health insurance to cover medical treatment costs is crucial. This is particularly important given the number of people who depend on work-place health insurance and the significant number of people who have lost their jobs during the pandemic.

Co-author Dr. Dawn E. Sugarman, a research psychologist in the Center of Excellence in Alcohol, Drugs, and Addiction at McLean Hospital, notes that:

“We hope this article will call attention to the pandemic’s effects on alcohol use and offer mitigating approaches to this under-recognized public health concern.”

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Nerve damage from neurodegenerative conditions, traumatic injuries, and certain eye conditions leads to disability and death for millions of people in the United States. Currently, doctors consider such damage irreversible.

However, researchers at The Ohio State University Wexner Medical Center have discovered a new type of human immune cell that appears to prevent and reverse nerve damage in the optic nerve and spinal cord.

This finding could allow researchers to create more advanced neurodegenerative immunotherapies.

These therapies might offer fresh hope to people with currently incurable neurological conditions, including Alzheimer’s diseasemultiple sclerosis, stroke, and Parkinson’s disease. They might also help treat central nervous system (CNS) damage from injury or infection.

“I treat patients who have permanent neurological deficits, and they have to deal with debilitating symptoms every day, “says Dr. Benjamin Segal, professor and chair of the Department of Neurology at The Ohio State College of Medicine and co-director of the Ohio State Wexner Medical Center’s Neurological Institute.

“So the idea of being able to restore neurological function and take that burden away from my patients is really amazing.”

Funded by the National Eye Institute (NEI), the National Institutes of Health (NIH), the Wings of Life Foundation (C.Y.), and the Dr. Miriam and Sheldon G. Adelson Research Foundation, the study appears in the journal Nature Immunology.

The emerging field of immunotherapy

Immunotherapy therapies alter the immune response by stimulating it or using the body’s own immune cells to treat disease. Over the past few decades, scientists have begun developing them to tackle a wide range of medical conditions.

Doctors already use immunotherapies to treat certain types of cancer. They help the immune system to recognize and destroy cancer cells.

Other researchers are investigating whether immunotherapy could help prevent or treat neurological disease.

Researchers have been extensively testing immunotherapies that increase the clearance rate of certain proteins whose accumulation has links with neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and dementia with Lewy bodies.

Scientists have already created T-cell mediated immunotherapy approaches that target proteins linked with these neurological diseases, such as amyloid-beta, tau, and alpha-synuclein proteins.

Immunotherapy may also present opportunities to prevent and treat nerve damage by activating alternative immune pathways in response to CNS damage.

2014 study found that anti-inflammatory or immunoregulating (M2) macrophages are critical for remyelination, which is a form of nerve repair.

The study

The researchers examined immune cells in fluids and spinal cord tissues collected from mice with optic and spinal nerve damage.

Within these fluids and tissues, the team found a unique type of granulocyte. Granulocytes are a category of white blood cells. Neutrophils are the most common kind of granulocytes.

Neutrophils are scavengers that help destroy pathogens or other unwanted particles in the body. The new type of granulocyte that the scientists identified behaved like an immature neutrophil.

This newly discovered granulocyte helped protect neural cells and tissues from damage in the mice. It also encouraged nerve cell regeneration by secreting a mix of beneficial growth compounds. The team also found a human cell line with similar neuroprotective properties.

“This type of cell actually secretes growth factors to rescue dying nerve cells. It can also stimulate the surviving nerve cells to grow new fibers once they’re severed or damaged in the [CNS], which is really unprecedented,” says Dr. Segal. “This can potentially lead to therapeutic breakthroughs for a wide range of conditions by repairing these nerve pathways.”

However, researchers have a long way to go before doctors can use immune cells, such as this newly discovered granulocyte, to treat humans.

The team’s first major hurdle will be figuring out how to harness the power of this new immune cell and enhance its natural healing effects by growing it in a laboratory setting. Next, they’ll have to prove their newly proposed therapy is both effective and safe in humans.

In the future, the team hopes that doctors can inject these novel cells into people with chronic cognitive deficits to slow down or halt degenerative decline.

Dr. Segal concludes that they have got a lot of work left to do to make their laboratory findings relevant in a clinical setting, but says he is optimistic about the road ahead:

“There’s so much that we’re learning at the bench that has yet to be translated to the clinic, but I think there’s huge potential for the future.”