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In a new trial, more than half of patients with persistent smell loss due to COVID-19 saw improvement with injections of platelet-rich plasma.

Early in the pandemic, when people with COVID-19 began reporting that they lost their sense of smell, Zara Patel figured as much. A professor of otolaryngology at Stanford Medicine, Patel has, for years, studied loss of smell as a symptom of viral infections.

“Many viruses can cause smell loss, so it wasn’t surprising to us as rhinologists when we found out that COVID-19 causes loss of smell and taste. It was almost expected,” she says. Patel also knew that the condition could last a while and that few effective treatments were available.

According to a 2022 survey by Patel and colleagues, about 15% of people who experienced smell loss from COVID-19 continued to have problems six months later. That’s roughly 9 million people in the US, and the number is growing. Many who report loss of smell also report loss of taste because smell is such a major component of how we experience food.

Now Patel’s team has tested a new treatment for long-term, COVID-19-related smell loss using injections of platelet-rich plasma derived from a patient’s own blood. In a trial of 26 participants, those who received the treatment were 12.5 times more likely to improve than patients who received placebo injections.

What is platelet-rich plasma?

Platelet-rich plasma is a concentrated form of plasma, the liquid portion of blood, with blood cells and other blood components removed. It’s rich in platelets and, most importantly, growth factors—compounds known to help regenerate tissue. Platelet-rich plasma has been purported to treat mild arthritis when injected into joints, reduce wrinkles when used on the face, and even regrow hair when injected into the scalp.

Patel was skeptical of such a cure-all but was intrigued by a study showing that platelet-rich plasma injections were as effective as surgery in treating carpal tunnel syndrome, which is caused by compressing and injuring a nerve in the wrist. She knew that COVID-19-related smell loss also was a neurological problem, in which long-term effects of the virus prevent nerves deep in the nasal cavity from regenerating correctly. These nerves connect to the brain and normally regenerate every three to four months.

“It’s a nerve damage and nerve regeneration issue that we’re dealing with,” she says.

How SARS-CoV-2 damages nerves

The SARS-CoV-2 virus doesn’t target nerve cells directly; it attacks supporting cells known as sustentacular cells, which have the ACE-2 receptor the virus uses to infect cells. These cells play a role in correct nerve regeneration, so persistent inflammation and damage to these cells may lead to long-term loss of function.

Patel had already completed a small pilot study demonstrating the safety of platelet-rich plasma injections in the nasal cavity when the pandemic hit, so she pivoted her plans for a larger trial to focus specifically on COVID-19-associated smell loss.

All participants had confirmed past COVID-19 infections and persistent smell loss lasting between 6 and 12 months. They also had to have already tried other treatments such as olfactory training and steroid rinses.

“I wanted to make sure that whatever intervention I was going to study was not just in place of or equivalent to the treatments we’re already doing, but a benefit above and beyond,” Patel says.

Half the participants received platelet-rich plasma injections into the tissue deep inside their nasal cavity every two weeks for six weeks, while the other half received placebo injections (of saline) on the same schedule. Neither the participants nor the researchers knew who received what.

Sniff, sniff

The researchers assessed smell ability using a standard olfactory test known as Sniffin’ Sticks. The test includes a range of odors, both pleasant (flowers) and terrible (rotten eggs), and participants are scored on their ability to identify the odors, tell odors apart, and determine their strength, for a possible score of 48.

When the researchers checked in with the participants three months after their first injection, those in the platelet-rich plasma group scored on average 6.25 points higher than they did before treatment, which was 3.67 points greater than the placebo group. They gained most in their ability to tell different odors apart, known as smell discrimination. At three months, 57.1% of the platelet-rich plasma group had shown a clinically significant improvement, compared with just 8.3% in the placebo group.

Interestingly, when the participants rated their own smell ability, both groups reported similar improvement. Patel says that prior studies have found that subjective improvement doesn’t always match up with objective improvement.

The improvements in the placebo group could in part be due to a placebo effect, Patel says, but they could also suggest that some spontaneous recovery can happen even after six months.

COVID-19 has brought attention to post-viral smell loss, and perhaps more appreciation of the role smell plays in our daily lives, Patel says. Though this study did not evaluate taste loss, the recovery of smell likely also would help with recovery of taste.

“People tell me all the time that they never realized how important their sense of smell and taste was to them and their quality of life until they lost it,” she says. “People say, ‘My life has gone gray.’”

Patel is now offering platelet-rich plasma injections to patients outside the trial.

“Our olfactory systems can be resilient,” Patel says. “But the sooner you perform some sort of definitive intervention, probably the better chance you have of improvement.”

The study appears in the International Forum of Allergy and Rhinology. Researchers from UC San Diego contributed to the study.

Source: Stanford University

Researchers report that the amount of emissions from gas-fired power could be cut by as much as 71% if a variety of mitigation options were used around the world.

About a quarter of the world’s electricity currently comes from power plants fired by natural gas. These contribute significantly to global greenhouse gas emissions (amounting to 10% of energy-related emissions according to the most recent figures from 2017) and climate change.

By gathering data from 108 countries around the world and quantifying the emissions by country, the new study estimates that total global carbon dioxide (CO2) emissions from the life cycle of gas-fired power is 39.68 billion tons each year.

“We were astonished by how large the potential reduction in greenhouse gases could be by 2050, and even by 2030,” says Sarah Jordaan, an associate professor in the civil engineering department and the Trottier Institute in Sustainability in Engineering and Design at McGill University and the first author of the paper.

“If natural gas is going to play a role in a low carbon future, even for a transitional period, there will be a need to improve efficiency in power plants and to cut methane emissions from natural gas production as well as to capture and store CO2.”

“We found that the most effective way to reduce greenhouse gas emissions was with carbon capture and storage, followed by making power plants more efficient,” adds Andrew Ruttinger, a PhD student in chemical and biomolecular engineering at Cornell University who participated in the research. “But the mitigation options that will be most successful in any given country will vary depending on the regional context and the existing infrastructure.”

The team calculated that the largest mitigation potential (39%) lies with five biggest emitters, the United States, Russia, Iran, Saudi Arabia, and Japan, all of whom, apart from Japan, are among the largest gas producers and consumers around the world.

“Climate change is a global challenge and achieving a low-carbon energy system points to the need for reducing emissions across the supply chain from gas extraction through end use,” says Arvind Ravikumar, a research associate professor in the petroleum and geosystems engineering department of Petroleum and Geosystems at the University of Texas at Austin.

“Our analysis demonstrates that significant efforts are needed to transition from current emissions levels, but also that by identifying the drivers of emissions in the gas supply chain, governments can take strategic, nationally-determined action to reduce their emissions.”

The research appears in Nature Climate Change.

Additional researchers from Carnegie Mellon, Johns Hopkins, the University of Texas at Austin, and the University of Maryland contributed to the work.

Source: McGill University

A new analysis of data from a yearlong weight-loss study identifies behaviors and biomarkers that contribute to short- and long-term weight loss.

Strictly following a diet—either healthy low-carb or healthy low-fat—was what mattered for short-term weight loss during the first six months. But people who maintained long-term weight loss for a year ate the same number of calories as those who regained weight or who did not lose weight during the second six months.

So what explains this difference?

According to the study, the bacteria living in your gut and the amounts of certain proteins your body makes can affect your ability to sustain weight loss. And some people, it turns out, shed more pounds on low-fat diets while others did better on low-carb diets.

The researchers have identified several biomarkers that predict how successful an individual will be at losing weight and keeping it off long-term. These biomarkers include signatures from the gut microbiome, proteins made by the human body, and levels of exhaled carbon dioxide. The researchers report their findings in the journal Cell Reports Medicine.

“Weight loss is enigmatic and complicated, but we can predict from the outset with microbiome and metabolic biomarkers who will lose the most weight and who will keep it off,” says Michael Snyder, professor and chair of genetics at the Stanford School of Medicine and co-senior author of the paper.

It’s not about your willpower

The data came from 609 participants who logged everything they ate for a year while following either a low-fat or low-carb diet made up of mostly high-quality, minimally processed foods. The researchers tracked participant exercise, how well they followed their diet, and the number of calories they took in.

“Your mindset should be on what you can include in your diet instead of what you should exclude.”

The study shows that just cutting calories or exercising was not enough to sustain weight loss over a year. To try and understand why, the team turned their focus to biomarkers of metabolism.

“We found specific microbiome ecologies and amounts of proteins and enzymes at the beginning of the study period—before people started following the diet—that indicated whether they would be successful at losing weight and keeping it off,” says Dalia Perelman, research dietician and co-lead author of the paper.

Throughout the study, the researchers measured the ratio of inhaled oxygen to exhaled carbon dioxide, known as a respiratory quotient, which serves as a proxy for whether carbohydrates or fats are the body’s primary fuel. A lower ratio means the body burns more fat, while a higher ratio means it burns more carbohydrates. So, those who started the diet with a higher respiratory quotient lost more weight on a low-carb diet.

“There are people who can be eating very few calories but still sustain their weight because of how their bodies metabolize fuels. It is not for lack of will: It is just how their bodies work,” Perelman says.

In other words, if your body prefers carbs and you’re predominately eating fat, it will be much harder to metabolize and burn off those calories.

“If you are following a diet that worked for someone you know and it is not working for you, it might be that that specific diet is not as suited for you,” adds Xiao Li, co-lead author of the paper and a former postdoctoral fellow at Stanford Medicine who is now at Case Western University.

Before biomarkers for weight loss are available

The predictive information gleaned from the gut microbiome, proteomic analysis, and respiratory quotient signatures lays the foundation for personalized diets. Snyder says he thinks tracking amounts of certain gut microbe strains will be a way for people to determine which diets are best for weight loss.

We’re not there yet, so until then, according to the researchers, the focus should be on eating high-quality foods that are unprocessed and low in refined flours and sugar.

The research team identified specific nutrients that were correlated with weight loss during the first six months. Low-carb diets should be based on monounsaturated fats—such as those that come from avocados, rather than from bacon—and high in vitamins K, C, and E. These vitamins are in vegetables, nuts, olives, and avocados. Low-fat diets should be high in fiber, such as is in whole grains and beans, and avoid added sugars.

“Your mindset should be on what you can include in your diet instead of what you should exclude,” Perelman says. “Figure out how to eat more fiber, whether it is from beans, whole grains, nuts, or vegetables, instead of thinking you shouldn’t eat ice cream. Learn to cook and rely less on processed foods. If you pay attention to the quality of food in your diet, then you can forget about counting calories.”

Source: Kimberlee D’Ardenne for Stanford University

A new gene expression-based diagnostic blood test can separate bacterial and viral infections with 90% accuracy, the first to meet standards set by the World Health Organization.

In developing countries, most antibiotic prescriptions are not only pointless—an estimated 70% to 80% of them are given for viral infections, which the medications don’t treat—they’re also harmful, as overuse of antibiotics accelerates antibiotic resistance.

“Accurately diagnosing whether a patient has a bacterial or viral infection is one of the biggest global health challenges.”

A similar problem exists in the United States, where an estimated 30% to 50% of antibiotic prescriptions are given for viral infections.

The new test could allow doctors around the world to quickly and accurately distinguish between bacterial and viral infections, thereby cutting down on antibiotic overuse. The test is based on how the patient’s immune system responds to an infection.

It is the first such diagnostic test validated in diverse global populations—accounting for a wider range of bacterial infections—and the only one to meet the accuracy targets set by the World Health Organization and the Foundation for Innovative New Diagnostics to address antibiotic resistance.

Those targets include at least 90% sensitivity (correctly identifying true positives) and 80% specificity (correctly identifying true negatives) to distinguish bacterial and viral infections.

The new test is described in a paper in Cell Reports Medicine.

“Antimicrobial resistance is continuously rising, so there has been a lot of effort to reduce inappropriate antibiotic usage,” says senior author Purvesh Khatri, associate professor of medicine and biomedical data science at Stanford University. “Accurately diagnosing whether a patient has a bacterial or viral infection is one of the biggest global health challenges.”

Existing methods include growing the pathogen in a Petri dish, which takes several days, or polymerase chain reaction (PCR) testing, which requires knowing the specific pathogen to look for.

That’s why in many cases, “Doctors prescribe antibiotics empirically,” Khatri says. “They say, ‘We’re going to give you an antibiotic and if you get better, you had a bacterial infection. If you don’t, you have a viral infection, and we’ll stop the antibiotic.’”

Immune system reaction

The test is one of a new crop of diagnostic tests that look at the host response—that is, how the patient’s immune system is reacting—to identify the type of infection. They measure the expression of certain genes involved in the host’s immune response.

“The immune system has been doing this for millions of years, constantly learning what is bacteria, what is virus and how to respond to it,” Khatri says. “Instead of looking for the bug itself, we can ask the immune system.”

However, because these host-response tests have been designed using data from Western Europe and North America, they fail to account for the types of infections that are prevalent in low- and middle-income countries. In particular, they have trouble distinguishing the more subtle differences between intracellular bacterial infections and viral infections.

“Epidemiologically, bacterial infections in developed countries are usually from bacteria that replicate outside the human cell,” Khatri says. These extracellular bacteria include E. coli and those that cause strep throat. In developing countries, common bacterial infections like typhus and tuberculosis are caused by intracellular bacteria, which replicate inside human cells, as do viruses.

“The immune system has a different response based on whether it’s an extracellular or intracellular bacterial infection,” Khatri says. “The reason it gets tricky is because once the bacteria are inside the cell, the pathways overlap with the viral infection response.”

Current host-response tests can distinguish extracellular bacterial infections from viral infections with more than 80% accuracy, but they can identify only 40% to 70% of intracellular infections.

Point-of-care test next?

To develop a diagnostic test that can separate both types of bacterial infections from viral infections, Khatri’s team used publicly available gene expression data from 35 countries. These included 4,754 samples from people of various ages, sexes, and races with known infections. The diversity of patients, infections and types of data is more representative of the real world, Khatri says.

Using machine learning and half of these samples, they identified eight genes that are expressed differently in bacterial versus viral infections. They validated their eight-gene test on the remaining samples and more than 300 new samples collected from Nepal and Laos.

They found that these eight genes could distinguish intracellular and extracellular bacterial infections from viral infections with high accuracy, achieving 90% sensitivity and 90% specificity. It is the first diagnostic test to meet (and exceed) the standards proposed by the World Health Organization and the Foundation for Innovative New Diagnostics.

“We’ve shown that this eight-gene signature has higher accuracy and more generalizability for distinguishing bacterial and viral infections, irrespective of whether they are intracellular or extracellular, whether a patient is in a developed or developing country, a man or a woman, an infant or an 80-year-old,” Khatri says.

He hopes the new diagnostic test can eventually be translated into a point-of-care test and adopted by doctors in both developed and developing countries, as it requires only a blood sample and can be performed in 30 to 45 minutes. His team has applied for a patent on the test.

Additional researchers from Mahosot Hospital and the University of Health Sciences in Lao People’s Democratic Republic, Dhulikhel Hospital in Nepal, the University of Oxford, and the University of Toronto contributed to the study.

The Bill and Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, the Department of Defense, the Ralph & Marian Falk Medical Research Trust, the Thomas C. and Joan M. Merigan Endowment at Stanford University, the Wellcome Trust of Great Britain, the National Science Foundation Graduate Research Fellowship, and the Stanford Graduate Fellowship funded the work.

Source: Stanford University