Obesity and metabolic syndrome are risk factors for severe influenza, COVID-19

July 15, 2020

Science Daily/American Society for Microbiology

Metabolic syndrome increases the risk of severe disease from viral infection, according to a review of the literature performed by a team of researchers from St. Jude Graduate School of Biomedical Sciences and the University of Tennessee Health Science Center, both in Memphis. The research appears this week in the Journal of Virology, a publication of the American Society for Microbiology.

Metabolic syndrome is a cluster of at least 3 co-occurring conditions that raise the risk of heart disease, stroke and type 2 diabetes mellitus (T2DM). These conditions include excess abdominal fat, high blood pressure, excess blood sugar, abnormalities of lipids (including excess triglycerides and cholesterol), insulin resistance and a proinflammatory state.

Multiple studies have shown that obesity is associated with increased severity of influenza A, higher viral titers in exhaled breath and prolonged transmission of the virus, according to the report. Changes in the viral population may abet the emergence of more pathogenic influenza variants, according to the report. Despite the fact that influenza vaccines generate robust antibody titers in obese subjects, obesity doubles the likelihood of developing influenza.

As with influenza virus, the Centers for Disease Control and Prevention recently recognized obesity as a risk factor for severe illness caused by SARS-CoV-2. "This is not surprising because excess body weight and fat deposition apply pressure to the diaphragm, which further increases the difficulty of breathing during a viral infection," the researchers write.

But the risk goes beyond the burden of excess weight. A recent study highlighted in the literature review looked at 174 diabetes patients with confirmed cases of COVID-19. The study found that these patients were at significantly higher risk for severe pneumonia compared to non-diabetic COVID-19 patients. CT scans revealed a greater severity of lung abnormalities in these patients.

There was also a profound increase in serum IL-6 levels, a predictive biomarker for disease severity, the investigators write. These data imply that SARS-CoV-2 causes severe disease in obese patients and in those with T2DM by inducing bilateral pneumonia and a cytokine storm that damages the lung epithelial-endothelial barrier. (The epithelium lines surfaces exposed to the outer environment, such as the respiratory tract, the endothelium lines inner pathways such as those of the vasculature.)

However, one hypothetical risk for patients with T2DM who have hypertension or heart disease appears not to be a problem, after all, according to the report. These patients are commonly treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). These increase expression of ACE2, the receptor that SARS-CoV-2 uses to gain entry into cells.

Clinicians and researchers were initially concerned that ACE inhibitors and ARBs could promote adhesion and entry of SARS-CoV-2 into host cells, thereby increasing the risk of severe COVID-19. Contrary to concerns, multiple studies now suggest that ACE inhibitors and ARBs do not lead to poorer outcomes in COVID-19 infection.

"Future research should seek to [determine] how metabolic abnormalities increase viral pathogenesis, as this information will play an essential role in global preparedness against emerging seasonal and pandemic virus strains," the investigators conclude.

https://www.sciencedaily.com/releases/2020/07/200715131234.htm

Common FDA-approved drug may effectively neutralize virus that causes COVID-19

Heparin could be used as a decoy to prevent SARS-CoV-2 from infecting human cells

July 15, 2020

Science Daily/Rensselaer Polytechnic Institute

A common drug, already approved by the Food and Drug Administration (FDA), may also be a powerful tool in fighting COVID-19, according to research published this week in Antiviral Research.

SARS-CoV-2, the virus that causes COVID-19, uses a surface spike protein to latch onto human cells and initiate infection. But heparin, a blood thinner also available in non-anticoagulant varieties, binds tightly with the surface spike protein, potentially blocking the infection from happening. This makes it a decoy, which might be introduced into the body using a nasal spray or nebulizer and run interference to lower the odds of infection. Similar decoy strategies have already shown promise in curbing other viruses, including influenza A, Zika, and dengue.

"This approach could be used as an early intervention to reduce the infection among people who have tested positive, but aren't yet suffering symptoms. But we also see this as part of a larger antiviral strategy," said Robert Linhardt, lead author and a professor of chemistry and chemical biology at Rensselaer Polytechnic Institute. "Ultimately, we want a vaccine, but there are many ways to combat a virus, and as we've seen with HIV, with the right combination of therapies, we can control the disease until a vaccine is found."

To infect a cell, a virus must first latch onto a specific target on the cell surface, slice through the cell membrane, and insert its own genetic instructions, hijacking the cellular machinery within to produce replicas of the virus. But the virus could just as easily be persuaded to lock onto a decoy molecule, provided that molecule offers the same fit as the cellular target. Once bound to a decoy, the virus would be neutralized, unable to infect a cell or free itself, and would eventually degrade.

In humans, SARS-CoV-2 binds to an ACE2 receptor, and the researchers hypothesized that heparin would offer an equally attractive target. In a binding assay, the researchers found that heparin bound to the trimeric SARS-CoV-2 spike protein at 73 picomoles, a measure of the interaction between the two molecules.

"That's exceptional, extremely tight binding," said Jonathan Dordick, a chemical and biological engineering professor at Rensselaer who is collaborating with Linhardt to develop the decoy strategy. "It's hundreds of thousands of times tighter than a typical antibody antigen. Once it binds, it's not going to come off."

Internationally recognized for his creation of synthetic heparin, Linhardt said that, in reviewing sequencing data for SARS-CoV-2, the team recognized certain motifs on the spike protein and strongly suspected it would bind to heparin. In addition to the direct binding assay, the team tested how strongly three heparin variants -- including a non-anticoagulant low molecular weight heparin -- bind to SARS-CoV-2, and used computational modeling to determine the specific sites where the compounds bind to the virus. All the results confirm heparin as a promising candidate for the decoy strategy. The researchers have subsequently initiated work on assessments of antiviral activity and cytotoxicity in mammalian cells.

"This isn't the only virus that we're going to confront in a pandemic," Dordick said. "We don't really have great antivirals, but this is a pathway forward. We need to be in a position where we understand how things like heparin and related compounds can block virus entry."

In previous work, a team led by Linhardt and Dordick demonstrated the decoy strategy on viruses with a mechanism similar to SARS-CoV-2. In 2019, the team created a trap for dengue virus, attaching specific aptamers -- molecules the viral latches will bind to -- precisely to the tips and vertices of a five-pointed star made of folded DNA. Floating in the bloodstream, the trap lights up when sprung, creating the world's most sensitive test for mosquito-borne diseases. In work prior to that, they created a synthetic polymer configured to match the sialic acid latch points on influenza virus, reducing influenza A mortality in mice from 100% to 25% over 14 days.

"This innovative approach to effectively trapping virusus is a prime example of how biotechnology approaches developed at Rensselaer are being brought forward to address challenging global health problems," said Deepak Vashishth, the director of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer, of which both Dordick and Linhardt are a part. "Professors Dordick and Linhardt have worked collaboratively across disciplines, and their research shows promise even beyond this current pandemic."

"Characterization of glycosaminoglycan and novel coronavirus (SARS-CoV-2) spike glycoprotein binding interactions" was published in Antiviral Research. At Rensselaer, Linhardt and Dordick were joined on the research by Fuming Zhang, and also by researchers at the University of California San Diego, Duke University, and the University of George, Athens with support from the National Institutes of Health.

https://www.sciencedaily.com/releases/2020/07/200715123203.htm

Researchers identify genetic factors that may influence COVID-19 susceptibility

July 15, 2020

Science Daily/Cleveland Clinic

A new Cleveland Clinic study has identified genetic factors that may influence susceptibility to COVID-19. Published today in BMC Medicine, the study findings could guide personalized treatment for COVID-19.

While the majority of confirmed COVID-19 cases result in mild symptoms, the virus does pose a serious threat to certain individuals. Morbidity and mortality rates rise dramatically with age and co-existing health conditions, such as cancer and cardiovascular disease. However, even young and otherwise healthy individuals have unpredictably experienced severe illness and death. These clinical observations suggest that genetic factors may influence COVID-19 disease susceptibility, but these factors remain largely unknown.

In this study, a team of researchers led by Feixiong Cheng, PhD, Genomic Medicine Institute, investigated genetic susceptibility to COVID-19 by examining DNA polymorphisms (variations in DNA sequences) in the ACE2 and TMPRSS2 genes. ACE2 and TMPRSS2 produce enzymes (ACE2 and TMPRSS2, respectively) that enable the virus to enter and infect human cells.

Looking at 81,000 human genomes from three genomic databases, they found 437 non-synonymous single-nucleotide variants in the protein-coding regions of ACE2 and TMPRSS2. They identified multiple potentially deleterious polymorphisms in both genes (63 in ACE2; 68 in TMPRSS2) that offer potential explanations for different genetic susceptibility to COVID-19 as well as for risk factors. Several ACE2 variants were found to be associated with cardiovascular and pulmonary conditions by potentially altering the angiotensinogen-ACE2. In addition, germline deleterious variants in the coding region of TMPRSS2, a key gene in prostate cancer, were found to occur in different cancer types, suggesting that oncogenic roles of TMPRSS2 may be linked to poor outcomes with COVID-19.

These findings demonstrate a possible association between ACE2 and TMPRSS2 polymorphisms and COVID-19 susceptibility, and indicate that a systematic investigation of the functional polymorphisms these variants among different populations could pave the way for precision medicine and personalized treatment strategies for COVID-19. However, all investigations in this study were performed in general populations, not with COVID-19 patient genetic data. Therefore, Dr. Cheng calls for a human genome initiative to validate his findings and to identify new clinically actionable variants to accelerate precision medicine for COVID-19.

"Because we currently have no approved drugs for COVID-19, repurposing already approved drugs could be an efficient and cost-effective approach to developing prevention and treatment strategies," Dr. Cheng said. "The more we know about the genetic factors influencing COVID-19 susceptibility, the better we will be able to determine the clinical efficacy of potential treatments."

https://www.sciencedaily.com/releases/2020/07/200715123153.htm

New research highlights increased loneliness in over-70s during COVID-19 pandemic

July 15, 2020

Science Daily/Trinity College Dublin

A joint report published by researchers at the Irish Longitudinal Study on Ageing (TILDA) and ALONE examines issues of loneliness and social isolation in older adults. The report offers fresh insight into the experiences of those over 70 who were advised to 'cocoon' as part of public health measures to curtail the spread of the COVID-19 virus. New data from ALONE which documents increased feelings of loneliness, anxiety and isolation in older adults throughout the pandemic, is compared with experiences of loneliness and isolation in older adults before the COVID-19 outbreak.

Previous research into this area has shown that strong social ties may protect people from emotional distress, cognitive decline, and physical disability, while loneliness and social isolation can cause harm to physical and psychological wellbeing. Both loneliness and social isolation have been strongly associated with poorer quality of life and other measures of well-being.

The TILDA study offers unique insights into the health, habits and experiences of older adults living in Ireland through its longitudinal research, examining a variety of key areas that affect older adults such as physical and mental health as well as economic and social factors. Research from TILDA highlights the prevalence of loneliness and social isolation in its nationally representative survey of participants which gives clear insight into the experiences of older people.

What does TILDA's research show prior to the pandemic?

• Over 70% of TILDA participants reported that they never or rarely feel lonely; less than 25% feel lonely some of the time while just 5% reported feeling lonely often.

• Of those living alone, 31% are rarely lonely, 32% sometimes lonely and 37% often lonely.

• Of those living with others, 49% are least lonely, 30% sometimes and 21% often lonely.

• Researchers point out that most older adults are not often lonely and appear quite resilient, while data from ALONE's helpline suggest that the COVID-19 pandemic has taken a toll on older people.

The rise of loneliness in a pandemic

Measures introduced to curb the spread of the COVID-19 virus, including physical distancing, and self-isolation particularly affected those over 70 who were 'cocooning'; disrupting daily routines and social interactions with friends and family. Following the outbreak of the virus, ALONE's Support and Telephone Befriending service continued remotely with volunteers calling and sending regular texts to older people with health and well-being tips and practical supports. Almost 500 smartphones were distributed to older adults with limited means of social interaction. Following an increase in calls for support, ALONE established a dedicated phoneline to provide help and services to vulnerable older adults who may have needed them. Report data from ALONE highlights increased feelings of loneliness and isolation amongst older people during the COVID-19 pandemic.

What does ALONE's research show?

• The ALONE national support line has received 26,174 calls during the period: March 9th to July 5th, 2020.

• 55% of callers were from the over 70s, the cohort advised to 'cocoon'.

• 75% of callers to the helpline were living alone.

• There has been an increase in callers who are putting off medical treatment or examination, including after falls.

• ALONE has seen a rise in callers reporting negative emotions, including suicidal ideation during the pandemic.

• Callers have most often requested support for their physical health, befriending, and emotional and mental health needs.

The data highlights that public health measures such as social distancing and cocooning to curb the spread of the virus has increased levels of loneliness and social isolation in older people. This may have a negative effect on the well-being of older adults and suggests that public policies should be developed to ensure that these issues are addressed. Researchers suspect that current physical distancing and social isolation measures will be most keenly felt by those who rely on community or church-based social participation and engagement.

A future research project led by TILDA in collaboration with ALONE will investigate and document the impact of the COVID-19 pandemic on the health and general well-being of older adults.

Professor Rose Anne Kenny, Principal Investigator of TILDA said:

''This collaborative report between ALONE and TILDA offers a unique perspective into how older adults have been affected by the COVID-19 pandemic. TILDA research shows that most older adults are not often lonely and highlights the resilience of older adults as they adapt to an ever-changing world. The world has witnessed how older adults have been disproportionately affected by the pandemic. ALONE's research provides front- line evidence that shows the true toll public health measures have had on older people with increased feelings of loneliness, anxiety and isolation. The impact of the pandemic is now being studied in the TILDA cohort and will be reported later this year. This will more precisely inform the impact of COVID-19 on loneliness and social isolation, and areas for policy intervention.''

Sean Moynihan, Chief Executive Officer of ALONE said:

''ALONE's coordinated National Response to the COVID-19 pandemic allowed us to respond with immediacy to the concerns newly emerging, and existing issues being elevated from older people. We worked to keep all our services operative through adaptation of their structures. The presence of this virus in society has further solidified existing issues while further alienating some older people, as we have seen extensive increases in loneliness through the isolation experienced from cocooning. We established a loneliness taskforce to ensure we were putting provisions in place to safeguard older people, presently, and into the future. Society needs to understand that loneliness can happen to anyone and can damage both your physical and mental health. It is distressing and we want to work towards breaking down this stigma. As Ireland's ageing population continues to develop, we must remember that there are several thousands of older people behind every percentage."

https://www.sciencedaily.com/releases/2020/07/200715111451.htm

New study shows SARS-CoV-2 viral load peaks in the early stages of disease

July 14, 2020

Science Daily/Elsevier

In a retrospective study, investigators from New York University Langone Health found that the quantity of SARS-CoV-2 (viral load) collected from patients in the emergency department is significantly higher in patients with fewer or milder symptoms who did not require hospitalization -- the opposite of what might be expected. Reporting in The American Journal of Pathology, published by Elsevier, they also found that a patient's history of cancer and cardiovascular disease is associated with higher viral loads even after adjusting for age.

The study was designed to determine possible associations between the viral load measured in patients positive for SARS-CoV-2 and their clinical parameters including severity of symptoms, hospital admission vs direct discharge, length of hospitalization, admission to the intensive care unit, length of need for oxygen support, and overall survival.

"It appears that the viral load peaks in the early stages of the disease. Although it is not associated with the duration of symptoms, their severity or outcome, it appears that the viral load is an important epidemiological surrogate marker of infectivity in mildly symptomatic and asymptomatic non-hospitalized patients, explained co-lead investigator Paolo Cotzia, MD, Assistant Professor, Department of Pathology, and Assistant Director, Center for Biospecimen Research and Development, NYU Langone Health, New York City, NY, USA.

"Whether the viral load in these patients stays the same or changes in later stages of the disease remains to be investigated and could provide further insights on the dynamics of viral replication."

Two hundred and five patients who visited the emergency department at a New York City tertiary care center with confirmed COVID-19 were included in the study. Nasopharyngeal samples were taken at the time of diagnosis. One hundred and sixty-five patients were discharged from the emergency department, and 40 patients were hospitalized. Non-hospitalized patients were younger overall, and other characteristics were similar across the group. The median duration from symptom onset to sample collection for the hospitalized group was five days compared with three days for the discharged patients.

Investigators found that the initial viral load was significantly lower in patients who required hospitalization compared to those who were discharged. The association remained significant even after adjustment for age, sex, race, body mass index, and other existing medical conditions. They also found that a higher viral load was associated with shorter duration of symptoms in all patients and was not associated with disease severity.

Co-lead investigator George Jour, MD, Assistant Professor, Department of Pathology and Department of Dermatology, Associate Director Molecular Pathology, NYU Langone Health, New York City, NY, USA, observed, "Another important finding of our study is that the initial nasopharyngeal viral load reflects the time from onset of symptoms and duration of symptoms. We found that higher viral loads are seen in mild rather than in severe disease because they appear to reflect the time lapsed from the onset of infection. Furthermore, higher viral loads correlate with the presence of cancer or cardiovascular diseases."

Although diagnostic viral load seems to have no prognostic utility for predicting outcomes from COVID-19, the investigators say it may be an important surrogate marker in mildly symptomatic, non-hospitalized patients. Their results support the concept that such patients may represent important sources of the virus. "Our study should increase awareness and should prompt the adherence to strict recommendation of social distancing and mask usage to avoid transmission," the investigators concluded.

https://www.sciencedaily.com/releases/2020/07/200714101257.htm

COVID-19 may attack patients' central nervous system

Researcher says depressed mood and anxiety may be symptoms of a COVID-19 impact on the brain

July 14, 2020

Science Daily/University of Cincinnati

Depressed mood or anxiety exhibited in COVID-19 patients may possibly be a sign the virus affects the central nervous system, according to an international study led by a University of Cincinnati College of Medicine researcher.

These two psychological symptoms were most closely associated with a loss of smell and taste rather than the more severe indicators of the novel coronavirus such as shortness of breath, cough or fever, according to the study.

"If you had asked me why would I be depressed or anxious when I am COVID positive, I would say it is because my symptoms are severe and I have shortness of breath or I can't breathe or I have symptoms such as cough or high fever," says Ahmad Sedaghat, MD, PhD, an associate professor and director of rhinology, allergy and anterior skull base surgery, in the UC College of Medicine's Department of Otolaryngology-Head and Neck Surgery.

"None of these symptoms that portended morbidity or mortality was associated with how depressed or anxious these patients were," explains Sedaghat, also a UC Health physician specializing in diseases of the nose and sinuses. "The only element of COVID-19 that was associated with depressed mood and anxiety was the severity of patients' loss of smell and taste. This is an unexpected and shocking result."

Sedaghat conducted a prospective, cross-sectional telephone questionnaire study which examined characteristics and symptoms of 114 patients who were diagnosed with COVID-19 over a six-week period at Kantonsspital Aarau in Aarau, Switzerland. Severity of the loss of smell or taste, nasal obstruction, excessive mucus production, fever, cough and shortness of breath during COVID-19 were assessed. The findings of the study are available online in The Laryngoscope.

First author of the study is Marlene M. Speth, MD, and other co-authors include Thirza Singer-Cornelius, MD; Michael Oberle, PhD; Isabelle Gengler, MD; and Steffi Brockmeier, MD.

At the time of enrollment in the study, when participants were experiencing COVID-19, 47.4% of participants reported at least several days of depressed mood per week while 21.1% reported depressed mood nearly every day. In terms of severity, 44.7% of participants reported expressing mild anxiety while 10.5% reported severe anxiety.

"The unexpected finding that the potentially least worrisome symptoms of COVID-19 may be causing the greatest degree of psychological distress could potentially tell us something about the disease," says Sedaghat. "We think our findings suggest the possibility that psychological distress in the form of depressed mood or anxiety may reflect the penetration of SARS-CoV-2, the virus that causes COVID-19, into the central nervous system."

Sedaghat says researchers have long thought that the olfactory tract may be the primary way that coronaviruses enter the central nervous system. There was evidence of this with SARS, or severe acute respiratory syndrome, a viral illness that first emerged in China in November 2002 and spread through international travel to 29 countries. Studies using mouse models of that virus have shown that the olfactory tract, or the pathway for communication of odors from the nose to the brain, was a gateway into the central nervous system and infection of the brain.

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"These symptoms of psychological distress, such as depressed mood and anxiety are central nervous system symptoms if they are associated only with how diminished is your sense of smell," says Sedaghat. "This may indicate that the virus is infecting olfactory neurons, decreasing the sense of smell, and then using the olfactory tract to enter the central nervous symptom."

Infrequent but severe central nervous system symptoms of COVID-19 such as seizures or altered mental status have been described, but depressed mood and anxiety may be the considerably more common but milder central nervous symptom of COVID-19, explains Sedaghat.

"There may be more central nervous system penetration of the virus than we think based on the prevalence of olfaction-associated depressed mood and anxiety and this really opens up doors for future investigations to look at how the virus may interact with the central nervous system," says Sedaghat.

For the cross-sectional telephone questionnaire study: The two-item Patient Health Question (PHQ-2) and the two-item Generalized Anxiety Disorder questionnaire (GAD-2) were used to measure depressed mood and anxiety level, respectively during COVID-19 and for participants' baseline pre-COVID-19 state.

https://www.sciencedaily.com/releases/2020/07/200714144739.htm

Engineered llama antibodies neutralize COVID-19 virus

July 13, 2020

Science Daily/The Rosalind Franklin Institute

Antibodies derived from llamas have been shown to neutralise the SARS-CoV-2 virus in lab tests, UK researchers announced today.

The team involves researchers from the Rosalind Franklin Institute, Oxford University, Diamond Light Source and Public Health England. They hope the antibodies -- known as nanobodies due to their small size -- could eventually be developed as a treatment for patients with severe COVID-19. The peer reviewed findings are published in Nature Structural & Molecular Biology.

Llamas, camels and alpacas naturally produce quantities of small antibodies with a simpler structure, that can be turned into nanobodies. The team engineered their new nanobodies using a collection of antibodies taken from llama blood cells. They have shown that the nanobodies bind tightly to the spike protein of the SARS-CoV-2 virus, blocking it from entering human cells and stopping infection.

Using advanced imaging with X-rays and electrons at Diamond Light Source and Oxford University, the team also identified that the nanobodies bind to the spike protein in a new and different way to other antibodies already discovered.

There is currently no cure or vaccine for COVID-19. However, transfusion of critically ill patients with serum from convalesced individuals, which contain human antibodies against the virus, has been shown to greatly improve clinical outcome. This process, known as passive immunisation, has been used for over 100 years, but it is not straightforward to identify the right individuals with the right antibodies and to give such a blood product safely. A lab-based product which can be made on demand would have considerable advantages and could be used earlier in the disease where it is likely to be more effective.

Professor James Naismith, Director of The Rosalind Franklin Institute and Professor of Structural Biology at Oxford University said: "These nanobodies have the potential to be used in a similar way to convalescent serum, effectively stopping progression of the virus in patients who are ill. We were able to combine one of the nanobodies with a human antibody and show the combination was even more powerful than either alone. Combinations are particularly useful since the virus has to change multiple things at the same time to escape; this is very hard for the virus to do. The nanobodies also have potential as a powerful diagnostic."

Professor Ray Owens from Oxford University, who leads the nanobody program at the Franklin, said: "This research is a great example of team work in science, as we have created, analysed and tested the nanobodies in 12 weeks. This has seen the team carry out experiments in just a few days, that would typically take months to complete. We are hopeful that we can push this breakthrough on into pre-clinical trials."

Professor David Stuart, from Diamond Light Source and Oxford University said: "The electron microscopy structures showed us that the three nanobodies can bind to the virus spike, essentially covering up the portions that the virus uses to enter human cells."

The team started from a lab-based library of llama antibodies. They are now screening antibodies from Fifi, one of the 'Franklin llamas' based at the University of Reading, taken after she was immunised with harmless purified virus proteins.

The team are investigating preliminary results which show that Fifi's immune system has produced different antibodies from those already identified, which will enable cocktails of nanobodies to be tested against the virus.

The Rosalind Franklin Institute is a new research institute funded through UK Research and Innovation's Engineering and Physical Sciences Research Council. The Franklin is leading the UK's work in the innovative field of nanobodies, whose tiny size and specificity make them perfect tools for scientific research, usually used to stabilise proteins for imaging. The Institute is named for the researcher Rosalind Franklin, who was born 100 years ago this year. Although famous for her contribution to the discovery of DNA, Franklin's later career turned to imaging virus structures, including polio.

Professor Naismith said: "2020 marks the centenary of Franklin's birth. As an institute named for a pioneer of biological imaging, we are proud to follow in her footsteps and continue her work in viruses, applied here to an unprecedented global pandemic. Franklin's work transformed biology, and our projects aspire to that same transformational effect."

https://www.sciencedaily.com/releases/2020/07/200713104334.htm

Preliminary study suggests tuberculosis vaccine may be limiting COVID-19 deaths

July 10, 2020

Science Daily/Virginia Tech

One of the emerging questions about the coronavirus that scientists are working to understand is why developing countries are showing markedly lower rates of mortality in COVID-19 cases than expected.

Research by Assistant Professor Luis Escobar of the College of Natural Resources and Environment and two colleagues at the National Institutes of Health suggests that Bacille Calmette-Guérin (BCG), a tuberculosis vaccine routinely given to children in countries with high rates of tuberculosis infection, might play a significant role in mitigating mortality rates from COVID-19. Their findings have been published in the Proceedings of the National Academy of Sciences.

"In our initial research, we found that countries with high rates of BCG vaccinations had lower rates of mortality," explained Escobar, a faculty member in the Department of Fish and Wildlife Conservation and an affiliate of the Global Change Center housed in the Fralin Life Sciences Institute. "But all countries are different: Guatemala has a younger population than, say, Italy, so we had to make adjustments to the data to accommodate those differences."

Escobar, working with NIH researchers Alvaro Molina-Cruz and Carolina Barillas-Mury, collected coronavirus mortality data from around the world. From that data, the team adjusted for variables, such as income, access to education and health services, population size and densities, and age distribution. Through all of the variables, a correlation held showing that countries with higher rates of BCG vaccinations had lower peak mortality rates from COVID-19.

One sample that stood out was Germany, which had different vaccine plans prior to the country's unification in 1990. While West Germany provided BCG vaccines to infants from 1961 to 1998, East Germany started their BCG vaccinations a decade earlier, but stopped in 1975. This means that older Germans -- the population most at risk from COVID-19 -- in the country's eastern states would have more protection from the current pandemic than their peers in western German states. Recent data shows this to be the case: western German states have experienced mortality rates that are 2.9 times higher than those in eastern Germany.

"The purpose of using the BCG vaccine to protect from severe COVID-19 would be to stimulate a broad, innate, rapid-response immunity," said Escobar, who noted that the BCG vaccines have already been shown to provide broad cross-protections for a number of viral respiratory illnesses in addition to tuberculosis.

Escobar stresses that the team's findings are preliminary, and that further research is needed to support their results and determine what the next steps should be for researchers. The World Health Organization noted that there is no current evidence that the BCG vaccine can protect people from COVID-19 infections, and stated that it does not currently recommend BCG vaccinations for the prevention of COVID-19. There are currently clinical trials underway to establish whether BCG vaccination in adults confers protection from severe COVID-19.

"We're not looking to advise policy with this paper," Escobar said. "This is, instead, a call for more research. We need to see if we can replicate this in experiments and, potentially, in clinical trials. We also need to come back to the data as we get more information, so we can reevaluate our understanding of the coronavirus pandemic."

Barillas-Mury, a chief researcher who specializes in mosquito-borne disease vectors, noted that establishing a link between BCG vaccines and COVID-19 case severity could result in attempts to stockpile doses of the BCG vaccine, placing countries with high tuberculosis rates at risk.

"If the BCG vaccine is protective, production would have to increase to meet the sudden spike in vaccine demand in order to prevent a delay in distribution to countries that very much need it to fight tuberculosis," she said.

While a direct correlation between BCG vaccinations and a reduction in coronavirus mortalities still needs to be understood more fully, researchers hold hope that the BCG vaccine might be able to provide at least short-term protections against severe COVID-19, particularly for front-line medical workers or high-risk patients. And, if BCG does provide short-term protection, there are longer term considerations about how countries could best utilize BCG vaccines to reduce mortality rates for future viral outbreaks that target the human respiratory system.

https://www.sciencedaily.com/releases/2020/07/200708121433.htm

Socio-economic, environmental impacts of COVID-19 quantified

Holistic study charts effects of the coronavirus on sectors and regions globally

July 10, 2020

Science Daily/University of Sydney

The first comprehensive study of the pandemic shows consumption losses amount to more than US$3.8 trillion, triggering full-time equivalent job losses of 147 million and the biggest-ever drop in greenhouse gas emissions.

The international group of researchers, using a global and highly detailed model, found that most directly hit was the travel sector and regions of Asia, Europe, the United States, with cascading multiplier effects across the entire world economy because of globalisation.

The loss of connectivity imposed to prevent the virus spreading triggers an economic 'contagion', causing major disruptions to trade, tourism, energy and finance sectors, while easing environmental pressures most in some of the hardest-hit areas.

This study focuses on 'live' data to 22 May (with the exception of air travel, for which only a 12-month forecast exists), differing from most assessments of the economic impacts of the pandemic based on scenario analyses and/or projections -- and it is the first to provide an overview of the combined economic, social and environmental impacts, including indirect effects, of the coronavirus.

The findings publish today in the international scientific journal PLOS ONE.

Key Reductions

• Consumption: US$3.8 trillion (4.2 percent ~ GDP of Germany)

• Jobs: 147m (4.2 percent of the global workforce)

• Income from wages and salaries: $2.1 trillion (6 percent)

• Most directly hit: US, China (mainland), air transport and related tourism

• Greenhouse gas emissions: 2.5Gt (4.6 percent) -- larger than any drop in human history*

• Other atmospheric emissions -- PM2.5: Dangerously fine particulate matter emissions fall 0.6 Mt (3.8 percent); SO2 & NOx: Sulfur dioxide emissions from burning fossil fuels -- which has been linked to asthma and chest tightness -- and emissions from nitrogen oxide -- from fuel combustion, for example, driving cars -- fall 5.1 Mt (2.9 percent).

Corresponding author Dr Arunima Malik, from Integrated Sustainability Analysis (ISA) and University of Sydney Business School, said the experience of previous financial shocks showed that, without structural change, environmental gains were unlikely to be sustained during economic recovery.

"We are experiencing the worst economic shock since the Great Depression, while at the same time we have experienced the greatest drop in greenhouse gas emissions since the burning of fossil fuels began," Dr Malik said.

"In addition to the sudden drop in climate-change inducing greenhouse gasses, prevented deaths from air pollution are of major significance.

"The contrast between the socio-economic and the environmental variables reveals the dilemma of the global socio-economic system -- our study highlights the interconnected nature of international supply chains, with observable global spillover effects across a range of industry sectors, such as manufacturing, tourism and transport."

The University of Sydney Vice-Chancellor Dr Michael Spence said it was wonderful to see significant applications come to life through a collaborative platform seeded a decade ago with University of Sydney funding.

"Thanks to pioneering work here at Sydney in collaboration with other world leaders in footprinting, it's now possible to simulate the world economy quickly and accurately to see how society and the environment are impacted by changes in our consumption," Dr Spence said.

"This research was conducted in the cloud-based Global MRIO Lab and it is these sorts of global, multidisciplinary collaborations that will help us tackle the complex issues of our time."

Research Using the Global MRIO Lab

To chart the world economy and post-disaster impacts using global multi-regional input-output (MRIO) analysis or GMRIO, researchers worked in the open-source Global MRIO Lab. This customisable database is an extension of the Australian Industrial Ecology Lab (IE Lab) led by the University of Sydney.

The advancement of GMRIO has underpinned the increasing popularity and uptake of so-called consumption-based accounting, or footprinting, which avoids loopholes such as 'carbon leakage' where pollution is externalised to the producers, rather than consumers of goods and services. The Global MRIO Lab includes data from statistical agencies, including National Accounts and Eurostat and international trade data such as UN Comtrade. The lab is powered by supercomputers calculating the impacts of international trade along billions of supply chains extending to 221 countries.

Input-output (I-O) models were developed in the 1930s by Nobel Prize Laureate Wassily Leontief to analyse the relationships between consumption and production in the economy; I-O or multi-regional input-output (MRIO) models take account of actual data, from I-O records worldwide. Global MRIO or GMRIO models now not only extend to global value chains (GVCs) incorporating all orders of production but are also able to answer flexible and complex questions to a high degree of accuracy within a relatively short time lag. Once assembled, tables can be quickly updated, limited only by the timeliness of the data to hand.

Lead author Professor Manfred Lenzen, also from ISA and a recent co-author of the "Scientists' warning on affluence," said that the Australian-funded and University of Sydney-led innovation of the IO Labs had really catalysed new research efficiency in Australia. "Whilst the Labs were initially developed by a dedicated team from eight Universities and the CSIRO, supported by the Australian Bureau of Statistics, there are now hundreds of users, answering questions ranging from building sustainable cities, avoiding food waste, and carbon-footprinting tourism, to hedging against major disasters such as tropical cyclones," said Professor Lenzen.

For this study into COVID-19, 38 regions in the world were analysed and 26 sectors. In order to incorporate as much information as possible, co-authors were allocated countries with which they had language skills and familiarity, with data translated from sources in 12 languages ranging from Arabic to Hindi and Spanish.

The international team of researchers are from: University of Sydney; Edinburgh Napier University; University of Queensland; UNSW Sydney; Ministry of Finance of the Republic of Indonesia; National Institute for Environmental Studies & Research Institute for Humanity and Nature, Japan; Yachay Tech University, Ecuador; Duke University; Beijing Normal University.

https://www.sciencedaily.com/releases/2020/07/200709141538.htm

Is your job killing you? Stress, lack of autonomy, ability can lead to depression, death

May 19, 2020

Science Daily/Indiana University

As millions continue working from home during the pandemic or are required to report to jobs as essential employees, many have raised questions about how these work conditions impact our health -- and not just as they relate to COVID-19.

A new study from the Indiana University Kelley School of Business finds that our mental health and mortality have a strong correlation with the amount of autonomy we have at our job, our workload and job demands, and our cognitive ability to deal with those demands.

"When job demands are greater than the control afforded by the job or an individual's ability to deal with those demands, there is a deterioration of their mental health and, accordingly, an increased likelihood of death," said Erik Gonzalez-Mulé, assistant professor of organizational behavior and human resources at the Kelley School and the paper's lead author.

"We examined how job control -- or the amount of autonomy employees have at work -- and cognitive ability -- or people's ability to learn and solve problems -- influence how work stressors such as time pressure or workload affect mental and physical health and, ultimately, death," he said. "We found that work stressors are more likely to cause depression and death as a result of jobs in which workers have little control or for people with lower cognitive ability."

On the other hand, Gonzalez-Mulé and his co-author, Bethany Cockburn, assistant professor of management at Northern Illinois University, found that job demands resulted in better physical health and lower likelihood of death when paired with more control of work responsibilities.

"We believe that this is because job control and cognitive ability act as resources that help people cope with work stressors," Gonzalez-Mulé said. "Job control allows people to set their own schedules and prioritize work in a way that helps them achieve their work goals, while people that are smarter are better able to adapt to the demands of a stressful job and figure out ways to deal with stress."

The study, "This Job Is (Literally) Killing Me: A Moderated-Mediated Model Linking Work Characteristics to Mortality," appears in the current issue of the Journal of Applied Psychology. It is a follow-up to previous research the pair published in 2017, which was the first study in the management and applied psychology fields to examine the relationship between job characteristics and mortality.

The researchers used data from 3,148 Wisconsin residents who participated in the nationally representative, longitudinal Midlife in the United States survey. Of those in their sample, 211 participants died during the 20-year study.

"Managers should provide employees working in demanding jobs more control, and in jobs where it is unfeasible to do so, a commensurate reduction in demands. For example, allowing employees to set their own goals or decide how to do their work, or reducing employees' work hours, could improve health," Gonzalez-Mulé said. "Organizations should select people high on cognitive ability for demanding jobs. By doing this, they will benefit from the increased job performance associated with more intelligent employees, while having a healthier workforce.

"COVID-19 might be causing more mental health issues, so it's particularly important that work not exacerbate those problems," Gonzalez-Mulé said. "This includes managing and perhaps reducing employee demands, being aware of employees' cognitive capability to handle demands and providing employees with autonomy are even more important than before the pandemic began."

https://www.sciencedaily.com/releases/2020/05/200519165842.htm