In the News

Another pandemic challenge for nurses: Sleep problems

Meat, MS and the microbiome

SARS-CoV-2 can remain active for longer than recommended quarantine period, study shows

Make-up of gut microbiome may be linked to long COVID risk

Stool Samples Reveal Microbial Enzyme Driving Bowel Disease

First of its kind study proves food intervention can be as effective as medications for lowering cholesterol Research reveals "food-as-medicine" to be a simple, viable solution to lowering cholesterol in many patients unable or unwilling to take statin drugs

Another pandemic challenge for nurses: Sleep problems

More than half of nurses had difficulty sleeping during the first six months of the COVID-19 pandemic-and getting less sleep increased their odds of experiencing anxiety and depression, according to a new study led by researchers at NYU Rory Meyers College of Nursing.

"Nurses are already at risk for higher rates of depression and insufficient sleep compared to other professions, thanks to the stress of patient care and the nature of shift work. The pandemic seems to have further exacerbated these issues to the detriment of nurses' well-being," said Amy Witkoski Stimpfel, PhD, RN, assistant professor at NYU Rory Meyers College of Nursing and the lead author of the study, which was published in the Journal of Occupational and Environmental Medicine.

Nurses have faced unparalleled challenges working on the frontlines of the COVID-19 pandemic, including staffing shortages, an early lack of personal protective equipment (PPE), and witnessing widespread suffering and death. Research is beginning to reveal the impact of these ongoing stressors on nurses' mental health and well-being.

In this study, the researchers surveyed 629 nurses and interviewed 34 nurses from June through August 2020. The nurses, who worked across healthcare settings in 18 states, were asked about their experiences working during the first six months of the pandemic in the U.S.

The survey revealed high rates of depression (22 percent), anxiety (52 percent), and insomnia (55 percent) among nurses. Notably, difficulty sleeping was both a contributing factor to and an outcome of poor mental health.

Only sleeping for five hours or less before a shift increased the odds of depression, anxiety, and insomnia. However, nurses also described how anxiety and thinking about stressful working conditions -- understaffing, being redeployed to a COVID unit, lack of PPE, and many patient deaths -- led to difficulty falling asleep and waking up at night. In addition to stress-related sleep problems, changes in nurses' work schedules from either working extra hours or abruptly switching between day and night shifts led to nurses getting fewer hours of sleep.

"We found that sleep problems were interwoven with anxiety and depressive symptoms," said Witkoski Stimpfel. "Prior research supports this bidirectional relationship between sleep and mental health. We know that getting sufficient sleep fosters mental and emotional resilience, while not getting enough sleep predisposes the brain to negative thinking and emotional vulnerability."

To better support nurses and their well-being, the researchers urge employers to take action to address work stress and factors that influence sleep. In addition to making sure that nurses have the resources like staffing, beds, and PPE to effectively do their jobs, employers can offer training on stress management and provide referrals to mental healthcare professionals for those in need. Employers should also pay attention to scheduling, ensuring nurses have time away from work, protecting them from excessive overtime hours and shifts that quickly switch between day and night, and offering flexible working arrangements.

"Our findings help us better understand the difficulty nurses are facing-and why some nurses are leaving their jobs or the field altogether-but also reveal opportunities for hospitals and other employers to support this critical workforce," said Witkoski Stimpfel.

Additional study authors include Lloyd Goldsamt and Victoria Vaughan Dickson of NYU Meyers and Lauren Ghazal of the University of Michigan. The research was supported by an NYU COVID-19 Research Catalyst grant.

Source New York University.

Meat, MS and the microbiome

Eating more meat, having less of certain bacteria in the gut, and more of certain immune cells in the blood, all link with multiple sclerosis, reports a team of researchers led by UConn Health and Washington University School of Medicine. The work, published in the 27 January issue of EBioMedicine, teased out subtle connections that could lead to a better understanding of the causes of the disease.

Multiple sclerosis (MS) is an autoimmune disease affecting fewer than 3 million people worldwide but costing $28 billion annually in the US alone -- and untold suffering. MS is more prevalent in specific regions, particularly the northern mid-latitudes, suggesting that geography is somehow linked to the disease, perhaps involving diet. But teasing out the exact relationships between diet, immune response and MS has been difficult. MS is most obviously an autoimmune disease in which the body attacks the insulation surrounding its nerves. When the insulation is damaged enough, the nerves begin to misfire and malfunction like wires with frayed insulation. But what triggers the body to attack the insulation in the nervous system in the first place is unknown.

More and more evidence has suggested that bacteria might be involved. The bacteria living in our guts can affect our immune system. And what we eat can affect the bacteria in our guts. Dr. Yanjiao Zhou at UConn Health School of Medicine collaborated with Dr. Laura Piccio from Washington University and now at the University of Sydney to study the gut microbiome, immune systems, diet, and blood metabolites in 49 volunteers -- 25 MS patients and 24 healthy controls -- to look for correlations that might be subtle but important.

"We found a number of gut bacteria associated with MS and severity of disability of MS patients. We also found increased autoimmune markers and signature metabolites in MS. But what is really interesting is how these systems connect with each other, and how diet is involved in these connections. Using multi-OMICS approaches, we try to close the loop and show the associations between multiple systems," says Zhou.

"This is the first study using an integrated approach to analyze the interplay between diet, gut microbiome, the immune system and metabolism and their contribution to disease pathogenesis and progression in people with MS. It opens a new modality to address future scientific questions by not looking at one individual factor, but at their complex interactions. This approach can lead to the identification of relevant networks that could be manipulated for disease prevention or therapeutic intervention," says Piccio.

The strongest systemic linkage the researchers found involved eating meat. Their analysis linked higher meat consumption to a decrease in the population of Bacteroides thetaiotaomicron in people's gut ecology. B. thetaiotaomicron is associated with digesting carbohydrates from vegetables.

Higher meat consumption, which was observed in the MS patients, was also linked to an increase in T-helper 17 cells in the immune system, and an increase in S-adenosyl-L-methionine (SAM) in their blood.

The relationship between meat eating and disability and the other factors was not deterministic; some healthy people eat a lot of meat. But the pattern of all the factors was suggestive that, in MS, something goes wrong with people's gut bacteria that dissociates them from the immune system, leading to heightened T-helper 17 cells and autoimmune attacks on the nervous system. And it tends to be associated with meat eating.

In the future, the team would like to expand the research to include more people, including those with a more severe form of MS. Eventually they hope to understand more of the cause-and-effect between diet, bacterial ecosystems in the gut, and immune response, and potentially help prevent or mitigate MS symptoms in people suffering from the disease.

Source: University of Connecticut.

SARS-CoV-2 can remain active for longer than recommended quarantine period, study shows

In a 38-year-old man who manifested mild symptoms of COVID-19 for 20 days, the novel coronavirus continued to be detected in his organism and to undergo mutations for 232 days. If he had not been given continuous medical care, maintained social distancing and worn a mask, he could have spread the virus throughout these seven months.

The atypical case of infection by SARS-CoV-2 was part of a study involving 38 Brazilian patients followed on a weekly basis between April and November 2020 by researchers affiliated with the Pasteur-USP Scientific Platform, a partnership between France's Pasteur Institute, the University of Sao Paulo (USP) and Oswaldo Cruz Foundation (Fiocruz) in Brazil. The patients were followed until they tested negative twice or three times consecutively by RT-qPCR.

The study was supported by FAPESP. An article reporting its findings is published in the journal Frontiers in Medicine.

It serves as an alert regarding the risk of limiting quarantine for COVID-19 patients to seven, ten or even 14 days after they test positive, as initially prescribed by protocols to combat the disease. It also reinforces the significance of vaccination, social distancing, and mask wearing.

"Of the 38 cases we tracked, two men and a woman were atypical in the sense that the virus was continuously detected in their organism for more than 70 days. Based on this result, we can say that about 8% of people infected by SARS-CoV-2 may be able to transmit the virus for more than two months, without necessarily manifesting any symptoms during the final stage of the infection," said Marielton dos Passos Cunha, first author of the article. The study was conducted while he was a postdoctoral intern at the Pasteur-USP Scientific Platform.

"We wanted to know if a period of 14 days was really long enough for the virus to stop being detectable. We concluded that it wasn't. It can take a month for a patient to test negative, and in some cases included in our study the patients remained positive for 71 to 232 days," said Paola Minoprio, one of the coordinators of the Platform and principal investigator for the study.

This is not the first evidence that the virus can remain active for longer than expected even in patients with mild symptoms. In early 2021, researchers at the University of São Paulo's Institute of Tropical Medicine (IMT-USP) in Brazil analyzed 29 samples of nasopharyngeal secretion from patients who tested positive for COVID-19. The material was collected at a public primary health center on the tenth day after the onset of symptoms, and inoculated into laboratory-grown cells. In 25% of the cases, the viruses present in the samples were capable of infecting the cells and replicating in vitro. In theory, therefore, other people could be infected if they came into contact with droplets of saliva expelled by 25% of these patients at the time the material was collected (more at: https://agencia.fapesp.br/35303/).

The risk appears to be even greater for people with compromised immune systems. In a paper published in June 2021, researchers at the same university's Medical School (FM-USP) described a case of infection that lasted at least 218 days.

The patient was about 40 years old and had undergone aggressive treatment for cancer before contracting COVID-19 (more at: https://agencia.fapesp.br/36281/).

Even so, this week the Brazilian Ministry of Health reduced the recommended period of self-isolation from ten to seven days for patients with mild or moderate symptoms, and to five days for people without symptoms if they test negative. At end-2021, the US Centers for Disease Control and Prevention (CDC) cut its recommendation from ten to five days in the case of asymptomatic patients provided they continue to wear a mask and test negative for COVID-19.

Intrahost mutations

In the study led by Minoprio, the difference between women and men in terms of the duration of viral activity was not significant (averaging 22 days and 33 days respectively). As for the three atypical cases, the virus remained detectable for 71 days in the woman and 81 days in one of the two men. None of them had comorbidities and all had mild symptoms of COVID-19.

The other atypical man continued to test positive for coronavirus for 232 days (April-November 2020), after which he tested negative three times by RT-qPCR. He has had HIV, the virus that causes AIDS, since 2018 but has no detectable viral load thanks to antiretroviral therapy.

"The fact that he's seropositive for HIV doesn't mean he's more susceptible to other infections, as he has undergone the therapy since he was diagnosed. His capacity to respond to an infection by another agent is comparable to that of any other individual, and indeed he did respond to coronavirus when infected. He isn't immunosuppressed [like cancer patients, people with autoimmune diseases or transplantees, for example]," Minoprio said.

According to the researchers, his HIV-positive status does not explain the long duration of his coronavirus infection. Many patients infected concurrently by HIV and SARS-CoV-2 would have to be compared with an appropriate control group in order to see if any genetic or immune traits in the host could be associated with such prolonged viral shedding.

The patient underwent weekly tests that detected the persistence of the infection, and samples of the virus were regularly sequenced to show that it was not a case of reinfection and that the virus not only continued to replicate but was also mutating.

The strategies used by the virus to escape the immune system during the infection were mapped, showing that viral load fell when there were more neutralizing antibodies, and that the virus was able to circumvent the body's defenses to build the load up again. The cycle repeated, forcing the production of more antibodies until viral load was again reduced.

"It's important to observe patients like this one because we can learn more about how the virus mutates and which mutations can give rise to variants of concern," Cunha said.

The patient in the study was infected by lineage B.1.1.28, which entered Brazil at the start of 2020. The researchers did not detect mutations in the virus isolated from the patient that could justify classifying it as more transmissible or more resistant to the immune system.

The Pasteur-USP Scientific Platform continues to investigate these and other cases. The 38 patients analyzed in the study led by Minoprio are part of a bank of blood and nasopharyngeal secretion samples collected from 721 people who manifested symptoms associated with this coronavirus.

"Fresh data will come from these samples, and we might be able to produce more palpable explanations for these atypical cases," Cunha said.

"These cases are further evidence that mask wearing and social distancing are the best ways to control the pandemic. If 14 days after testing positive a person isn't tested again, they may still be shedding active viruses and be able to infect others, contributing to community transmission," Minoprio said. "It's crucial to keep track of infected people so we can find out more about mutations, novel variants, and the transmissibility of SARS-CoV-2."

Make-up of gut microbiome may be linked to long COVID risk

The make-up of the gut microbiome may be linked to a person's risk of developing 'long COVID' many months after initial infection with SARS-CoV-2, the virus responsible for COVID-19 infection, suggests research published online in the journal Gut.

Microbiome 'profiling' might help identify those who are most susceptible to developing the condition, suggest the researchers.

Post acute COVID-19 syndrome, dubbed 'long COVID', is characterised by complications and/or persistent symptoms weeks and months after initial COVID-19 infection.

It is relatively common, with up to 3 out of 4 people reporting at least one symptom 6 months after recovery from COVID-19 infection. Fatigue, muscle weakness, and insomnia are the most commonly reported symptoms.

An exaggerated immune system response, cell damage, or the physiological consequences of a critical illness may contribute to the development of long COVID. But it's not clear exactly what causes it, or why some people seem to be more susceptible, say the researchers.

A growing body of evidence has implicated the gut microbiome-the trillions of bacteria, fungi, and other microbes that inhabit the digestive tract-in COVID-19 severity.

And given that the gut has a major role in immunity, a disordered immune response to COVID-19 infection, induced by resident microbes, may affect the recovery process too.

The researchers therefore wanted to find out if the make-up of the gut microbiome might be linked to long COVID, defined as at least one persistent symptom 4 weeks after clearance of SARS-CoV-2 from the body.

They tracked changes in the gut microbiome of 106 patients with varying degrees of COVID-19 severity, treated at 3 different hospitals between February and August 2020, and in a comparison group of 68 people who didn't have COVID-19, over the same period.

They did this by analysing participants' stool samples. Among the 106 patients with COVID-19, stool samples were collected on admission (68), and again after 1 month (64) and after 6 months (68). Stool samples were also collected from 11 patients 9 months later.

The researchers checked for the presence of the 30 most commonly reported long COVID symptoms 3 and 6 months after initial COVID-19 infection. Aerobic capacity and endurance, an indicator of long COVID, was also measured in a 6-minute distance walk test.

The average age of the patients with COVID-19 infection was 48; just over half were women. Most (81%) had mild to moderately severe infection; 25 were treated with antibiotics.

Long COVID was reported in 86 (81%) of these patients at 3 months and in 81 (76.5%) at 6 months. The most common symptoms at 6 months were fatigue (31%), poor memory (28%), hair loss (22%), anxiety (21%) and sleep disturbances (21%).

There were no significant differences in potentially influential factors, such as age, gender, prevalence of underlying conditions, use of antibiotics or antiviral drugs, or COVID-19 severity between patients with and without long COVID, 6 months after initial infection.

While initial viral load wasn't associated with long COVID, their gut microbiome differed from that of patients without long COVID and those who hadn't had COVID-19 infection.

These patients had a less diverse and abundant microbiome; the gut microbiome of patients who didn't develop long COVID was similar to that of those who hadn't had COVID-19.

Among the bacteria species found in patients with long COVID, 28 were reduced and 14 were enriched both at hospital admission and at 3 and 6 months after hospital discharge.

At 6 months, patients with long COVID had significantly fewer 'friendly' F. prausnitzii, and Blautia obeum and a greater abundance of 'unfriendly' Ruminococcus gnavus and Bacteroides vulgatus than people who hadn't had COVID-19.

On the other hand, the gut microbiome of those who didn't develop long COVID showed only 25 changes in bacteria species at hospital admission, and this recovered completely after 6 months.

The researchers then looked at the make-up of the gut microbiome to see if was associated with different categories of long COVID symptoms: respiratory; neuropsychiatric (headache, dizziness, loss of taste and smell, anxiety, poor concentration, disrupted sleep, low mood, poor memory, blurred vision); gastrointestinal; skin (hair loss); musculoskeletal; and fatigue.

Eighty one bacterial species were associated with different categories of long COVID and many species were associated with more than two categories of persistent symptoms.

For example, at 6 months, persistent respiratory symptoms were strongly associated with several opportunistic 'unfriendly' microbes, including Streptococcus anginosus, Streptococcus vestibularis, Streptococcus gordonii and Clostridium disporicum.

And several species known to boost immunity, including Bifidobacterium pseudocatenulatum, F. prausnitzii, R. inulinivorans and Roseburia hominis, were depleted in those with long COVID at 6 months.

Similarly, several 'unfriendly' bacteria species were associated with poorer performance on the 6-minute walk test among those with long COVID.

At hospital admission, the diversity and richness of gut bacteria in patients who subsequently developed long COVID was significantly lower than that of patients who didn't, suggesting that particular gut microbial profiles may indicate heightened susceptibility, say the researchers.

This is an observational study, and as such can't establish cause. And only a small number of participants were included in the study. But the findings echo those of other research, implicating a disordered gut microbiome in a range of long term conditions, point out the researchers.

And they conclude: "In summary, altered gut microbiome composition is strongly associated with persistent symptoms in patients with COVID-19 up to 6 months after clearance of SARS-CoV-2 virus.

"Considering the millions of people infected during the ongoing pandemic, our findings are a strong impetus for consideration of microbiota modulation to facilitate timely recovery and reduce the burden of post-acute COVID-19 syndrome."

Stool Samples Reveal Microbial Enzyme Driving Bowel Disease

Ulcerative colitis, a subtype of inflammatory bowel disease, is a chronic ailment of the colon affecting nearly one million individuals in the United States. It is thought to be linked to disruptions in the gut microbiome - the bacteria and other microbes that live inside us - but no existing treatments actually target these microorganisms.

In a study publishing in Nature Microbiology, researchers at University of California San Diego School of Medicine have identified a class of microbial enzymes that drive ulcerative colitis, and have demonstrated a potential route for therapeutic intervention.

"Studies continue to show correlations between gut health and microbial constituents, but these trends don't exactly explain how the bacteria cause disease or what we can do about it," said study co-senior author David J. Gonzalez, PhD, associate professor of pharmacology at UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. "This is the first study with experimental evidence that pinpoints a specific microbe driving ulcerative colitis, the protein class it expresses, and a promising solution."

Gonzalez and his collaborators are leaders in multi-omics - an approach that combines state-of-the-art genomics, proteomics, metabolomics and peptidomics to uncover the contents of a biological sample with unprecedented detail. The process of "digitizing" a sample allows the team to examine its biology at multiple scales and develop new hypotheses of disease progression.

"What makes UC San Diego special is our highly collaborative science, where world leaders in all the different 'omics' can come together to break new ground," said study co-senior author Rob Knight, PhD, professor and director of the Center for Microbiome Innovation at UC San Diego. "This study showcases the power of combining these technologies to explore biology in new ways."

To study the gut microbiome, Gonzalez said the most useful biological sample is patient stool. It is also far less invasive to collect than more traditional blood or tissue samples.

"Once we had all the technology to digitize the stool, the question was, is this going to tell us what's happening in these patients? The answer turned out to be yes. We've shown that stool samples can be extremely informative in guiding our understanding of disease. Digitizing fecal material is the future."

The team found that roughly 40 percent of ulcerative colitis patients show an overabundance of proteases - enzymes that break down other proteins - originating from the gut resident Bacteroides vulgatus. They then showed that transplanting high-protease feces from human patients into germ-free mice induced colitis in the animals. However, the colitis could be significantly reduced by treating the mice with protease inhibitors.

The team suggested that a stressor in the gut, such as nutrient deprivation, may increase protease production in an attempt to use proteins as an alternative nutrient source. However, these bacterial proteases may be damaging to the colonic epithelium or lining of the colon, allowing an influx of immune cells to then further exacerbate the disease.

Authors hope the study will inspire future work to confirm this hypothesis and develop protease-blocking drugs for use in humans. Now that a specific family of proteins has been implicated in this form of ulcerative colitis, they said, clinicians may also one day use antibody tests to quickly discern if a patient is a good candidate for protease treatment.

The researchers said their approach to stool analysis and multi-omic data integration might also be used to study other diseases, including diabetes, cancer, rheumatic and neurological conditions.

Co-authors include: Robert H. Mills, Parambir S. Dulai, Yoshiki Vázquez-Baeza, Consuelo Sauceda, Romana R. Gerner, Lakshmi E. Batachari, Mario Malfavon Ochoa, Qiyun Zhu, Kelly Weldon, Greg Humphrey, Marvic Carrillo-Terrazas, Lindsay DeRight Goldasich, MacKenzie Bryant, Manuela Raffatellu, Robert A. Quinn, Andrew T. Gewirtz, Hiutung Chu, William J. Sandborn and Pieter C. Dorrestein, all at UC San Diego, and Noëmie Daniel and Benoit Chassaing at Université de Paris.

This research was funded, in part, by the National Institutes of Health (grants P30 DK120515, T32 DK007202), the American Gastroenterology Association, and the Collaborative Center of Multiplexed Proteomics at UC San Diego.

Source: University of California San Diego Health

First of its kind study proves food intervention can be as effective as medications for lowering cholesterol Research reveals "food-as-medicine" to be a simple, viable solution to lowering cholesterol in many patients unable or unwilling to take statin drugs

High cholesterol, a major risk factor for heart disease, affects nearly 94 million Americans, and 1 in 2 adults over the age of 50. While most doctors are quick to prescribe drugs (like statins) for treatment, a new study points to an effective food-based alternative for the millions of Americans impacted -- especially those who may be concerned about medication side effects.

The results of a groundbreaking study, published in the Journal of Nutrition, demonstrated that for many individuals a "food as medicine" approach can be as effective as medications for cholesterol lowering, without the need for drastic lifestyle changes.

"Based on the outcomes seen in our study, using this type of food as medicine approach expands the options for medical professionals and patients," said Stephen Kopecky, M.D, FACC, cardiologist and Director of the Statin Intolerance Clinic at Mayo Clinic. "Many patients who are unwilling or unable to take statin drugs may be able to help manage their high cholesterol, or hyperlipidemia with a realistic food-based intervention."

Substituting only a small portion of what hyperlipidemic patients were eating with Step One Foods (a twice per day dosed eating system with products precisely formulated to help lower LDL cholesterol), researchers found rapid and highly significant cholesterol reductions. Ultimately, participants saw an average 9% decrease in LDL (bad) cholesterol within 30 days, with some experiencing more than 30% LDL cholesterol reductions.

This first of its kind free-living multicenter international study was conducted at Mayo Clinic in Rochester, Minnesota and Richardson Centre at the University of Manitoba in Winnipeg, Manitoba. The study which followed a randomized, double-blind crossover design, was conducted by Soumya Alias, University of Manitoba; Peter J. H. Jones, Richardson Centre for Functional Foods and Nutraceuticals; Elizabeth Klodas, M.D., founder and Chief Medical Officer of Step One Foods and Stephen L. Kopecky, M.D, Mayo Clinic.

During the intervention phase, participants ate an assortment of whole food based snacks from Step One Foods - ranging from chocolate bars to strawberry-banana smoothies - that were made entirely from real ingredients, such as walnuts, and are known to positively impact cholesterol profiles. These study foods were specifically formulated to deliver a nutrient compendium of whole food fiber, plant sterols, ALA omega 3 fatty acids and antioxidants. Participants were instructed to consume these snacks in exchange for similar foods they were consuming already.

The researchers also compared the results of Step One Foods with comparable leading grocery stores brands that are considered "better for you" foods. Each participant consumed these leading brands for 30 days. No cholesterol reductions were seen during this phase of the study.

"Nutrition contributes to 5 of the 7 modifiable risk factors for heart disease, but getting patients to change diet is incredibly challenging," said Elizabeth Klodas MD, FACC. "This study underscores what's possible when we succeed. The implications of attaining such a significant cholesterol impact from a small food based intervention are profound. We could change the health of our country in 30 d