COVID-19: Immune system derails
August 6, 2020
Science Daily/DZNE - German Center for Neurodegenerative Diseases
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction -- rather, the immune response is caught in a continuous loop of activation and inhibition. Experts from Charité -- Universitätsmedizin Berlin, the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE), the Helmholtz Centre for Infection Research (HZI) and the German Center for Infection Research (DZIF), along with colleagues from a nationwide research network, present these findings in the scientific journal Cell.
Most patients infected with the coronavirus SARS-CoV-2 show mild or even no symptoms. However, 10 to 20 percent of those affected develop pneumonia during the course of COVID-19 disease, some of them with life-threatening effects. "There is still not very much known about the causes of these severe courses of the disease. The high inflammation levels measured in those affected actually indicate a strong immune response. Clinical findings, however, rather tend to indicate an ineffective immune response. This is a contradiction," says Joachim Schultze, professor at the University of Bonn and research group leader at the DZNE. "We therefore assume that although immune cells are produced in large quantities, their function is defective. That is why we examined the blood of patients with varying degrees of COVID-19 severity," explains Leif Erik Sander, Professor of Infection Immunology and Senior Physician Charité's Medical Department, Division of Infectious Diseases and Respiratory Medicine.
High-precision methods
The study was carried out within the framework of a nationwide consortium -- the "German COVID-19 OMICS Initiative" (DeCOI) -- resulting in the analysis and interpretation of the data being spread across various teams and sites. Joachim Schultze was significantly involved in coordinating the project. The blood samples came from a total of 53 men and women with COVID-19 from Berlin and Bonn, whose course of disease was classified as mild or severe according to the World Health Organization classification. Blood samples from patients with other viral respiratory tract infections as well as from healthy individuals served as important controls.
The investigations involved the use of single-cell OMICs technologies, a collective term for modern laboratory methods that can be used to determine, for example, the gene activity and the amount of proteins on the level of single, individual cells -- thus with very high resolution. Using this data, the scientists characterized the properties of immune cells circulating in the blood -- so-called white blood cells. "By applying bioinformatics methods on this extremely comprehensive data collection of the gene activity of each individual cell, we could gain a comprehensive insight of the ongoing processes in the white blood cells," explains Yang Li, Professor at the Centre for Individualised Infection Medicine (CiiM) and Helmholtz Centre for Infection Research (HZI) in Hannover. "In combination with the observation of important proteins on the surface of immune cells, we were able to decipher the changes in the immune system of patients with COVID-19," adds Birgit Sawitzki, Professor at the Institute of Medical Immunology on Campus Virchow-Klinikum.
"Immature" cells
The human immune system comprises a broad arsenal of cells and other defense mechanisms that interact with each other. In the current study, the focus was on so-called myeloid cells, which include neutrophils and monocytes. These are immune cells that are at the very front of the immune response chain, i.e. they are mobilized at a very early stage to defend against infections. They also influence the later formation of antibodies and other cells that contribute to immunity. This gives the myeloid cells a key position.
"With the so-called neutrophils and the monocytes we have found that these immune cells are activated, i.e. ready to defend the patient against COVID-19 in the case of mild disease courses. They are also programmed to activate the rest of the immune system. This ultimately leads to an effective immune response against the virus," explains Antoine-Emmanuel Saliba, head of a research group at the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg.
But the situation is different in severe cases of COVID-19, explains Sawitzki: "Here, neutrophils and monocytes are only partially activated and they do not function properly. We find considerably more immature cells that have a rather inhibitory effect on the immune response." Sander adds: "The phenomenon can also be observed in other severe infections, although the reason for this is unclear. Many indications suggest that the immune system stands in its own way during severe courses of COVID-19. This could possibly lead to an insufficient immune response against the corona virus, with a simultaneous severe inflammation in the lung tissue."
Approaches to therapy?
The current findings could point to new therapeutic options, says Anna Aschenbrenner from the LIMES Institute at the University of Bonn: "Our data suggest that in severe cases of COVID-19, strategies should be considered that go beyond the treatment of other viral diseases." The Bonn researcher says that in the case of viral infections one does not actually want to suppress the immune system. "If, however, there are too many dysfunctional immune cells, as our study shows, then one would very much like to suppress or reprogram such cells." Jacob Nattermann, Professor at the Medical Clinic I of the University Hospital Bonn and head of a research group at the DZIF, further explains: "Drugs that act on the immune system might be able to help. But this is a delicate balancing act. After all, it's not a matter of shutting down the immune system completely, but only those cells that slow down themselves, so to speak. In this case these are the immature cells. Possibly we can learn from cancer research. There is experience with therapies that target these cells."
Nationwide team effort
In view of the many people involved, Schultze emphasizes the cooperation within the research consortium: "As far as we know, this study is one of the most comprehensive studies to date on the immune response in COVID-19 based on single cell data. The parallel analysis of two independent patient cohorts is one of the strengths of our study. We analyzed patient cohorts from two different sites using different methods and were thus able to validate our findings directly. This is only possible if research data is openly shared and cooperation is based on trust. This is extremely important, especially in the current crisis situation."
https://www.sciencedaily.com/releases/2020/08/200806111822.htm
COVID-19: The long road to recovery
August 6, 2020
Science Daily/University of Leeds
Researchers have identified a pattern of longer-term symptoms likely to be experienced by people who were hospitalised with the COVID-19 infection.
They include fatigue, breathlessness, psychological distress -- including problems with concentration and memory -- and a general decline in quality of life.
Some patients, particularly those who had been in intensive care, had symptoms associated with cases of PTSD (post-traumatic stress disorder).
The findings provide the first detailed insight into problems facing patients recovering from COVID-19 in the UK.
Dr Manoj Sivan, Associate Clinical Professor at the University of Leeds and a Consultant in Rehabilitation Medicine at Leeds General Infirmary, supervised the research project. He said: "COVID-19 is a new illness and we have very little information on longer term problems in individuals after discharge from hospital."
"The emerging evidence is that for some, the road to recovery may take months and it is vital specialist rehabilitation is on hand to support them. This research gives an important insight into patient needs, and that will help shape services in the community."
The findings -- Post-discharge symptoms and rehabilitation needs in survivors of COVID-19 infection: a cross-sectional evaluation -- have been published in the Journal of Medical Virology.
Dr Stephen Halpin, Senior Research Fellow at the University of Leeds and Consultant with Leeds Teachings Hospitals NHS Trust, said: "This research follows our previous work of predicting COVID-19 patients' long-term needs based on previous coronavirus outbreaks of SARS in 2002 and MERS in 2012. The health problems are similar but on a larger scale given the number of people affected."
The research team -- involving multidisciplinary specialists from the University of Leeds, Leeds Teaching Hospitals NHS Trust, Leeds Community Healthcare NHS Trust and Leeds Beckett University -- followed 100 people recovering from COVID-19, four-to-eight weeks after being discharged from hospital in Leeds.
The COVID-19 survivors were divided into two groups: those who had become critically ill and needed intensive care -- 32 people were in this category; and those who were treated on a ward without needing intensive care -- 68 people were in this category.
Patients were contacted by a member of the hospital's rehabilitation team and asked a series of questions about their recovery and symptoms they were still experiencing.
Results
The most prevalent symptom was fatigue. More than 60 percent of people who had been treated on a ward reported fatigue, and one-third of them described it as moderate or severe. For patients who had been in intensive care, 72 percent reported fatigue. Of those, more than half said it was moderate or severe.
The second most common symptom was breathlessness. People in both groups said they had feelings of breathlessness which had not existed before they contracted COVID-19. This was higher in the group that had been the most ill, the intensive care group versus those who had been treated in a ward -- 65.6 percent versus 42.6 percent.
The third most prevalent symptoms were neuropsychological. The research survey found that almost one quarter of the people who had been on a ward and just under a half of the people who had been in intensive care had some of the symptoms of PTSD.
Writing in the paper, the researchers said: "PTSD symptoms are a well-recognised component of post- intensive care unit syndrome caused by a variety of factors including fear of dying, invasive treatment, pain, delirium, inability to communicate, weakness, immobility, and sensory problems and sleep deprivation."
More than two-thirds (68.8 percent) of patients in the intensive care group and just under half (45.6 percent) of the other group said their overall quality of life had deteriorated.
The researchers say the rehabilitation needs of patients who did not require hospital care need to be further investigated and they are working on understanding this in future research.
https://www.sciencedaily.com/releases/2020/08/200806122820.htm
Young kids could spread COVID-19 as much as older children and adults
Findings important to nationwide conversations on reopening schools and daycare
July 30, 2020
Science Daily/Ann & Robert H. Lurie Children's Hospital of Chicago
A study from Ann & Robert H. Lurie Children's Hospital of Chicago discovered that children younger than 5 years with mild to moderate COVID-19 have much higher levels of genetic material for the virus in the nose compared to older children and adults.
Findings, published in JAMA Pediatrics, point to the possibility that the youngest children transmit the virus as much as other age groups. The ability of younger children to spread COVID-19 may have been under-recognized given the rapid and sustained closure of schools and daycare during the pandemic.
"We found that children under 5 with COVID-19 have a higher viral load than older children and adults, which may suggest greater transmission, as we see with respiratory syncytial virus, also known as RSV," says lead author Taylor Heald-Sargent, MD, PhD, pediatric infectious diseases specialist at Lurie Children's and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "This has important public health implications, especially during discussions on the safety of reopening schools and daycare."
Dr. Heald-Sargent and colleagues analyzed 145 cases of mild to moderate COVID-19 illness within the first week of symptom onset. They compared the viral load in three age groups -- children younger than 5 years, children 5-17 years and adults 18-65 years.
"Our study was not designed to prove that younger children spread COVID-19 as much as adults, but it is a possibility," says Dr. Heald-Sargent. "We need to take that into account in efforts to reduce transmission as we continue to learn more about this virus."
https://www.sciencedaily.com/releases/2020/07/200730141324.htm
Pregnant Black and Hispanic women five times more likely to be exposed to coronavirus
July 29, 2020
Science Daily/University of Pennsylvania School of Medicine
Black and Hispanic pregnant women in Philadelphia are five times as likely as white and Asian women to have been exposed to the novel coronavirus, according to a new study led by Scott Hensley, PhD, an associate professor of Microbiology in the Perelman School of Medicine at the University of Pennsylvania, and Karen Marie Puopolo, MD, PhD, an associate professor of Pediatrics and neonatologist at the Children's Hospital of Philadelphia. The study was published today in Science Immunology.
"Pregnant women are fairly representative of community exposure, and these data provide more evidence, on top of what we already know with COVID-19, that health and socio-economic equity are inextricably linked," Hensley said, "Hopefully, this will help lead to policies that address these inequities."
The research team measured levels of SARS-CoV-2 antibodies to estimate rates of exposure to the novel coronavirus in pregnant women cared for at two Philadelphia hospitals. They found that, overall, 6.2 percent of these women possessed antibodies to the virus, but with significant variation across racial and ethnic groups -- 9.7 percent in Black women, 10.4 percent in Hispanic/Latina women, 2.0 percent in White/Non-Hispanic women, and 0.9 percent in Asian women.
Researchers said these data can inform clinical practice and care for pregnant women during the coronavirus pandemic, and be used to better understand the prevalence of the virus in the community, and how socio-economic factors and inequities may affect its spread.
"Identifying the disparity in virus exposure will ideally help lead to the discovery of what is causing these differences, including factors rooted in systemic racism, and inform public health measures aimed at preventing further infections," Puopolo said.
As of June 2020 -- the time period encompassed in this study -- there were 23,160 confirmed cases of COVID-19 in the city of Philadelphia, which has a population size of nearly 1.6 million people. This suggests an infection rate of approximately 1.4 percent, which is more than 4 times lower than the estimates based on the research team's serological data.
Researchers analyzed 1,293 women who gave birth between April and June at Pennsylvania Hospital and the Hospital of the University of Pennsylvania, which combined represent 50 percent of live births during that time in Philadelphia. The research team's serological test utilized a SARS-CoV-2 spike protein receptor binding domain antigen and a modified ELISA protocol. Researchers used samples stored at the Penn Medicine Biobank collected from 834 people prior to the pandemic and 31 people who recovered from known Covid-19 infections to test the efficacy of their antibody test. The researchers also tested samples from 140 pregnant women collected before the pandemic. Based on these data, the overall false positive rate is ~1.0 percent in the serological assay used for this study.
The researchers caution that the clinical meaning of the detected antibody remains unknown. Additionally, estimates of virus prevalence need to be interpreted carefully until studies directly comparing pregnant women and the general population are completed.
https://www.sciencedaily.com/releases/2020/07/200729151652.htm
COVID-19 provides rare opportunities for studying natural and human systems
July 29, 2020
Science Daily/Stanford University
Like the legendary falling apple that hit Isaac Newton and led to his groundbreaking insight on the nature of gravity, COVID-19 could provide unintended glimpses into how complex Earth systems operate, according to a new Stanford-led paper. The perspective, published July 29 in Nature Reviews Earth & Environment, hypothesizes outcomes of unprecedented changes in human activity wrought by worldwide sheltering orders, and outlines research priorities for understanding their short and long-term implications. Getting it right could revolutionize how we think about issues as broad as greenhouse gas emissions, regional air quality, and the global economy's connection to poverty, food security and deforestation, according to the researchers. It could also help ensure an economically, socially and environmentally sustainable recovery from the coronavirus pandemic while helping prevent future crises.
"Without distracting from the most important priority -- which is clearly the health and well-being of people and communities -- the current easing of the human footprint is providing a unique window into the impacts of humans on the environment, including a number of questions that are critical for effective public policy," said lead author Noah Diffenbaugh, the Kara J Foundation Professor at Stanford's School of Earth, Energy & Environmental Sciences.
For example, the question of how much electrifying the vehicle fleet will improve air quality has until now relied heavily on theoretical arguments and computer models. The scale of recent emissions reductions, however, provides an opportunity to use atmospheric observations to check just how accurate those models are in simulating the impact of pollution-reduction interventions such as electric vehicle incentives.
Predicting pandemic outcomes
The researchers note that although many of the initial impacts of COVID sheltering, such as clear skies resulting from reduced pollutant emissions, could be perceived as beneficial to the environment, the longer-term impacts -- particularly related to the economic recession -- are less clear. To understand the impacts across both short and long timescales, they propose focusing on cascading effects along two pathways: (1) energy, emissions, climate and air quality; and (2) poverty, globalization, food and biodiversity.
Given the complex interactions along these pathways, the researchers emphasize the need for techniques that can bring together multiple lines of evidence to reveal causes and effects. This includes bolstering and expanding coordinated efforts to study the impacts of the pandemic, including safe deployment of environmental sensors that can track changing conditions, computer models that simulate Earth's response to the sheltering measures and solutions-oriented research trials that lend insight into human behavior and decision making. The authors also call for a coordinated data repository where many different kinds of data can be made openly available to the public in a uniform format.
"Almost overnight, people across the world had to change the way they live, the way they work -- with many facing loss of income -- commute, buy food, educate their children and other energy-consuming behaviors," said Inês Azevedo, an associate professor of energy resources engineering in Stanford's School of Earth, Energy & Environmental Sciences. "It's critical for us to better understand how future societal disruptions and catastrophes could affect interactions among energy systems and other systems that serve society."
Understanding the human response
A key factor in understanding how the pandemic's effects play out is its influence on human behavior and decision making.
"Human behavior contributes to, but is also affected by, changes in the Earth system, and COVID-19 is creating new challenges for ensuring people and corporations act to protect the planet," said co-author Margaret Levi, the Sara Miller McCune Director of Stanford's Center for Advanced Study in the Behavioral Sciences and a professor of political science. "While government was not a central focus in this paper, it clarifies the roles that laws, regulations and investments play in the safety of the food supply and food workers, emissions controls and many other aspects of the health of the Earth and its inhabitants."
Some of the pandemic's most lasting impacts on climate and air quality could occur via insights it provides into the calculation of policy parameters that measure the value that individuals and society place on different environmental trade-offs. The COVID-19 crisis is making these tradeoffs more explicit, the researchers point out. This is because governments, communities and individuals are making historic decisions reflecting underlying preferences for current and future consumption, as well as the tradeoff between different types of economic activity and individual and collective risk.
These decisions can help quantify the parameters that are routinely used in environmental policymaking (such as the cost of human lives lost to air pollution or of climate change associated with carbon dioxide emissions). As those updated parameters are incorporated into actual policy decisions, they will have lasting effects on the regulations that impact the long-term trajectory of climate and air quality.
Studying policy interventions designed to prevent socio-environmental damage -- such as the role of poverty in driving deforestation -- could also help vulnerable people weather poverty shocks from COVID-19 by providing a deeper understanding of how and where poverty and environmental degradation are most tightly linked. The researchers propose using the kinds of solution-oriented research trials that were awarded this year's Nobel Prize in Economics to study whether interventions such as payments for protection of natural resources are effective in staving off deforestation, over-fishing and other environmental damages.
"COVID-19 poses some of the biggest challenges we have faced in the last century," said paper co-author Chris Field, the Perry L. McCarty Director of the Stanford Woods Institute for the Environment and Melvin and Joan Lane Professor for Interdisciplinary Environmental Studies. "With every challenge, there are opportunities for learning, and this paper provides a map for expanding the set of opportunities."
https://www.sciencedaily.com/releases/2020/07/200729114809.htm
Racial disparities in COVID-19–related deaths exist beyond income differences in large U.S. cities
July 28, 2020
Science Daily/NYU Langone Health / NYU School of Medicine
While data and news reports show that Black and Hispanic communities are disproportionately affected by the 2019 Coronavirus Disease (COVID-19) pandemic, the role that neighborhood income plays in COVID-19 deaths is less clear. New analyses by a team of researchers at NYU Grossman School of Medicine examine the interplay between race/ethnicity and income on COVID-19 cases and related deaths in 10 major U.S. cities. The researchers found that non-white counties had higher cumulative incidences and deaths compared to predominantly white counties -- and this was true for both low-income and high-income communities.
The findings -- recently published online in JAMA Network Open -- suggest that racial disparities in COVID-19 cases and deaths exist beyond what can be explained by differences in poverty rates. The researchers found that even among communities with higher median income, predominantly non-white communities still bore a greater burden of the virus -- almost three times the incidence and deaths -- compared to neighborhoods that identified as majority white. Yet income also plays an important contributing role. Indeed, the starkest racial/ethnic contrast between majority non-white and predominantly white counties was found when restricted to low-income counties only, where residents from predominantly non-white communities died from COVID-19 at nine times the rate as those living in predominantly white counties.
"While we expected to see greater numbers of COVID-19 cases and deaths in predominantly non-white, low-income communities, we were surprised that this relationship still held even after we accounted for poverty rates," said Samrachana Adhikari, PhD, assistant professor, Department of Population Health, NYU Grossman School of Medicine, and lead author of the study. "Given our findings, we believe that structural racism may explain these racial disparities in number of cases and deaths noted in Black counties."
How the Study was Conducted
Using publicly available data from the 2018 U.S. Census Small Areas Income and Poverty Estimates program, the Centers for Disease Control, and state health departments, the researchers examined cumulative COVID-19 cases and deaths per 100,000 across 158 urban counties (accounting for 64 percent of confirmed COVID-19 cases) spanning 10 large U.S. cities: New York City, Boston, New Orleans, Detroit, Los Angeles, Atlanta, Miami, Chicago, Philadelphia, and Seattle. Using the census data, the team linked median income and proportion of non-white residents in each county and used statistical analysis to identify differences in cumulative incidents and death, and their association with neighborhood race/ethnicity and poverty levels. All data analyzed included COVID-19 cases and deaths observed through May 10, 2020.
"We have known for decades that racism kills. Racism is a public health issue which has been implicated in the racial gap in mortality and in health outcomes," says Gbenga Ogedegbe, MD, MPH, professor of Population Health and Medicine at NYU Langone and one of the study's co-authors.
"Because the differences in COVID-19 cases and mortality cannot be explained by poverty alone, our findings give credence to our hypothesis that structural racism underlies the disproportionately higher rates of COVID-19 infections and alarmingly high rates of deaths in predominantly Black communities. The fact that non-white residents died from the virus at higher rates than white residents in both wealthier and poorer communities should be a major alarm bell to policymakers at the national and local government levels, academic medical centers, and the country at large," says Ogedegbe.
One of the study's limitations, according to Adhikari, is that it covers only large metropolitan areas and that the data analyzed are aggregated at the county level. More granular data at the individual level, as well as a breakdown of residents by race and ethnicity, would provide greater insight into the drivers of this troubling association, as well as expose most affected neighborhoods in need of more robust public health interventions, says Adhikari.
https://www.sciencedaily.com/releases/2020/07/200728113539.htm
Researchers identify evolutionary origins of SARS-CoV-2
July 28, 2020
Science Daily/Penn State
By reconstructing the evolutionary history of SARS-CoV-2, the virus that is responsible for the COVID-19 pandemic, an international research team of Chinese, European and U.S. scientists has discovered that the lineage that gave rise to the virus has been circulating in bats for decades and likely includes other viruses with the ability to infect humans. The findings have implications for the prevention of future pandemics stemming from this lineage.
"Coronaviruses have genetic material that is highly recombinant, meaning different regions of the virus's genome can be derived from multiple sources," said Maciej Boni, associate professor of biology, Penn State. "This has made it difficult to reconstruct SARS-CoV-2's origins. You have to identify all the regions that have been recombining and trace their histories. To do that, we put together a diverse team with expertise in recombination, phylogenetic dating, virus sampling, and molecular and viral evolution."
The team used three different bioinformatic approaches to identify and remove the recombinant regions within the SARS-CoV-2 genome. Next, they reconstructed phylogenetic histories for the non-recombinant regions and compared them to each other to see which specific viruses have been involved in recombination events in the past. They were able to reconstruct the evolutionary relationships between SARS-CoV-2 and its closest known bat and pangolin viruses. Their findings appear today (July 28) in Nature Microbiology.
The researchers found that the lineage of viruses to which SARS-CoV-2 belongs diverged from other bat viruses about 40-70 years ago. Importantly, although SARS-CoV-2 is genetically similar (about 96%) to the RaTG13 coronavirus, which was sampled from a Rhinolophus affinis horseshoe bat in 2013 in Yunnan province, China, the team found that it diverged from RaTG13 a relatively long time ago, in 1969.
"The ability to estimate divergence times after disentangling recombination histories, which is something we developed in this collaboration, may lead to insights into the origins of many different viral pathogens," said Philippe Lemey, principal investigator in the Department of Evolutionary and Computational Virology, KE Leuven.
The team found that one of the older traits that SARS-CoV-2 shares with its relatives is the receptor-binding domain (RBD) located on the Spike protein, which enables the virus to recognize and bind to receptors on the surfaces of human cells.
"This means that other viruses that are capable of infecting humans are circulating in horseshoe bats in China," said David L. Robertson, professor of computational virology, MRC-University of Glasgow Centre for Virus Research.
Will these viruses be capable of jumping directly from bats into humans or will an intermediate species be required to make the leap? According to Robertson, for SARS-CoV-2, other research groups incorrectly proposed that key evolutionary changes occurred in pangolins.
"SARS-CoV-2's RBD sequence has so far only been found in a few pangolin viruses," said Robertson. "Furthermore, the other key feature thought to be instrumental to SARS-CoV-2's ability to infect humans -- a polybasic cleavage site insertion in the Spike protein -- has not yet been seen in another close bat relative of the SARS-CoV-2 virus. Yet, while it is possible that pangolins may have acted as an intermediate host facilitating transmission of SARS-CoV-2 to humans, no evidence exists to suggest that pangolin infection is a requirement for bat viruses to cross into humans. Instead, our research suggests that SARS-CoV-2 likely evolved the ability to replicate in the upper respiratory tract of both humans and pangolins."
The team concluded that preventing future pandemics will require better sampling within wild bats and the implementation of human disease surveillance systems that are able to identify novel pathogens in humans and respond in real time.
"The key to successful surveillance," said Robertson, "is knowing which viruses to look for and prioritizing those that can readily infect humans. We should have been better prepared for a second SARS virus."
Boni added, "We were too late in responding to the initial SARS-CoV-2 outbreak, but this will not be our last coronavirus pandemic. A much more comprehensive and real-time surveillance system needs to be put in place to catch viruses like this when case numbers are still in the double digits."
https://www.sciencedaily.com/releases/2020/07/200728113512.htm
Face coverings do not lead to false sense of security
July 27, 2020
Science Daily/University of Cambridge
Existing limited evidence suggests that wearing face coverings to protect against COVID-19 does not lead to a false sense of security and is unlikely to increase the risk of infection through wearers foregoing other behaviours such as good hand hygiene, say researchers from the University of Cambridge and King's College London.
Writing in BMJ Analysis, the researchers say that the concept of 'risk compensation' is itself the greater threat to public health as it may discourage policymakers from implementing potentially effective measures, such as wearing face coverings.
Wearing face coverings, particularly in shared indoor spaces, is now mandated or recommended in more than 160 countries to reduce transmission of SARS-CoV-2, the virus that causes COVID-19. Worn correctly, face coverings can reduce transmission of the virus as part of a set of protective measures, including maintaining physical distance from others and good hand hygiene.
While it is not clear how much of an effect face coverings have, scientists have urged policymakers to encourage the wearing of face coverings because the risks are minimal while the potential impact is important in the context of the COVID-19 pandemic.
However, early in the pandemic, the World Health Organization warned that wearing face coverings could "create a false sense of security that can lead to neglecting other essential measures such as hand hygiene practices." This type of behaviour is known as 'risk compensation'.
A team led by Professor Dame Theresa Marteau at the Behaviour and Health Research Unit, University of Cambridge, has examined the evidence for risk compensation to see whether concerns might be justified in the context of face coverings to reduce transmission of SARS-CoV-2.
The idea behind risk compensation is that people have a target level of risk they are comfortable with and they adjust their behaviour to maintain that level risk. At an individual level, risk compensation is commonplace: for example, people run for longer to offset an eagerly anticipated indulgent meal and a cyclist may wear a helmet to cycle at speed.
At a population level, evidence for risk compensation is less clear. A commonly-cited example is the mandated wearing of bike helmets purportedly leading to an increase in the number of bike injuries and fatalities. Another often-cited example is the introduction of HIV pre-exposure prophylaxis (PrEP) and HPV vaccination purportedly leading to an increase in unprotected sex.
Professor Marteau and colleagues say the results of the most recent systematic reviews -- a technique that involves examining all available evidence on a topic -- do not justify the concerns of risk compensation for either of these examples. In fact, for HPV vaccination, the opposite effect was found: those who were vaccinated were less likely to engage in unprotected sexual behaviour as measured by rates of sexually transmitted infection.
At least 22 systematic reviews have assessed the effect of wearing a mask on transmission of respiratory virus infections. These include six experimental studies, involving over 2,000 households in total -- conducted in community settings that also measured hand hygiene. While none of the studies was designed to assess risk compensation or looked at social distancing, their results suggest that wearing masks does not reduce the frequency of hand washing or hand sanitising. In fact, in two studies, self-reported rates of hand washing were higher in the groups allocated to wearing masks.
The team also found three observational studies that showed people tended to move away from those wearing a mask, suggesting that face coverings do not adversely affect physical distancing at least by those surrounding the wearer. However, they say that as none of these studies have been peer-reviewed, they should be treated with caution.
"The concept of risk compensation, rather than risk compensation itself, seems the greater threat to public health through delaying potentially effective interventions that can help prevent the spread of disease," said Professor Marteau.
"Many public health bodies are coming to the conclusion that wearing a face covering might help reduce the spread of SARS-CoV-2, and the limited evidence available suggests their use doesn't have a negative effect on hand hygiene," added co-author Dr James Rubin from the Department of Psychological Medicine, King's College London.
In their article, the team argue that it is time to lay risk compensation theory to rest. Professor Barry Pless from McGill University, Montreal, Canada, once described it as "a dead horse that no longer needs to be beaten." The authors go further, saying "this dead horse now needs burying to try to prevent the continued threat it poses to public health, from by slowing the adoption of more effective interventions."
https://www.sciencedaily.com/releases/2020/07/200727114706.htm
How COVID-19 causes smell loss
Coronavirus illustration (stock image). Credit: © Production Perig / stock.adobe.com
Olfactory support cells, not neurons, are vulnerable to novel coronavirus infection
July 24, 2020
Science Daily/Harvard Medical School
Loss of smell, or anosmia, is one of the earliest and most commonly reported symptoms of COVID-19. A new study identifies the olfactory cell types most vulnerable to infection by the novel coronavirus. Surprisingly, sensory neurons involved in smell are not among the vulnerable cell types.
Temporary loss of smell, or anosmia, is the main neurological symptom and one of the earliest and most commonly reported indicators of COVID-19. Studies suggest it better predicts the disease than other well-known symptoms such as fever and cough, but the underlying mechanisms for loss of smell in patients with COVID-19 have been unclear.
Now, an international team of researchers led by neuroscientists at Harvard Medical School has identified the olfactory cell types most vulnerable to infection by SARS-CoV-2, the virus that causes COVID-19.
Surprisingly, sensory neurons that detect and transmit the sense of smell to the brain are not among the vulnerable cell types.
Reporting in Science Advances on July 24, the research team found that olfactory sensory neurons do not express the gene that encodes the ACE2 receptor protein, which SARS-CoV-2 uses to enter human cells. Instead, ACE2 is expressed in cells that provide metabolic and structural support to olfactory sensory neurons, as well as certain populations of stem cells and blood vessel cells.
The findings suggest that infection of nonneuronal cell types may be responsible for anosmia in COVID-19 patients and help inform efforts to better understand the progression of the disease.
"Our findings indicate that the novel coronavirus changes the sense of smell in patients not by directly infecting neurons but by affecting the function of supporting cells," said senior study author Sandeep Robert Datta, associate professor of neurobiology in the Blavatnik Institute at HMS.
This implies that in most cases, SARS-CoV-2 infection is unlikely to permanently damage olfactory neural circuits and lead to persistent anosmia, Datta added, a condition that is associated with a variety of mental and social health issues, particularly depression and anxiety.
"I think it's good news, because once the infection clears, olfactory neurons don't appear to need to be replaced or rebuilt from scratch," he said. "But we need more data and a better understanding of the underlying mechanisms to confirm this conclusion."
A majority of COVID-19 patients experience some level of anosmia, most often temporary, according to emerging data. Analyses of electronic health records indicate that COVID-19 patients are 27 times more likely to have smell loss but are only around 2.2 to 2.6 times more likely to have fever, cough or respiratory difficulty, compared to patients without COVID-19.
Some studies have hinted that anosmia in COVID-19 differs from anosmia caused by other viral infections, including by other coronaviruses.
For example, COVID-19 patients typically recover their sense of smell over the course of weeks -- much faster than the months it can take to recover from anosmia caused by a subset of viral infections known to directly damage olfactory sensory neurons. In addition, many viruses cause temporary loss of smell by triggering upper respiratory issues such as stuffy nose. Some COVID-19 patients, however, experience anosmia without any nasal obstruction.
Pinpointing vulnerability
In the current study, Datta and colleagues set out to better understand how sense of smell is altered in COVID-19 patients by pinpointing cell types most vulnerable to SARS-CoV-2 infection.
They began by analyzing existing single-cell sequencing datasets that in total catalogued the genes expressed by hundreds of thousands of individual cells in the upper nasal cavities of humans, mice and nonhuman primates.
The team focused on the gene ACE2, widely found in cells of the human respiratory tract, which encodes the main receptor protein that SARS-CoV-2 targets to gain entry into human cells. They also looked at another gene, TMPRSS2, which encodes an enzyme thought to be important for SARS-CoV-2 entry into the cell.
The analyses revealed that both ACE2 and TMPRSS2 are expressed by cells in the olfactory epithelium -- a specialized tissue in the roof of the nasal cavity responsible for odor detection that houses olfactory sensory neurons and a variety of supporting cells.
Neither gene, however, was expressed by olfactory sensory neurons. By contrast, these neurons did express genes associated with the ability of other coronaviruses to enter cells.
The researchers found that two specific cell types in the olfactory epithelium expressed ACE2 at similar levels to what has been observed in cells of the lower respiratory tract, the most common targets of SARS-CoV-2, suggesting a vulnerability to infection.
These included sustentacular cells, which wrap around sensory neurons and are thought to provide structural and metabolic support, and basal cells, which act as stem cells that regenerate the olfactory epithelium after damage. The presence of proteins encoded by both genes in these cells was confirmed by immunostaining.
In additional experiments, the researchers found that olfactory epithelium stem cells expressed ACE2 protein at higher levels after artificially induced damage, compared with resting stem cells. This may suggest additional SARS-CoV-2 vulnerability, but it remains unclear whether or how this is important to the clinical course of anosmia in patients with COVID-19, the authors said.
Datta and colleagues also analyzed gene expression in nearly 50,000 individual cells in the mouse olfactory bulb, the structure in the forebrain that receives signals from olfactory sensory neurons and is responsible for initial odor processing.
Neurons in the olfactory bulb did not express ACE2. The gene and associated protein were present only in blood vessel cells, particularly pericytes, which are involved in blood pressure regulation, blood-brain barrier maintenance and inflammatory responses. No cell types in the olfactory bulb expressed the TMPRSS2 gene.
Smell loss clue
Together, these data suggest that COVID-19-related anosmia may arise from a temporary loss of function of supporting cells in the olfactory epithelium, which indirectly causes changes to olfactory sensory neurons, the authors said.
"We don't fully understand what those changes are yet, however," Datta said. "Sustentacular cells have largely been ignored, and it looks like we need to pay attention to them, similar to how we have a growing appreciation of the critical role that glial cells play in the brain."
The findings also offer intriguing clues into COVID-19-associated neurological issues. The observations are consistent with hypotheses that SARS-CoV-2 does not directly infect neurons but may instead interfere with brain function by affecting vascular cells in the nervous system, the authors said. This requires further investigation to verify, they added.
The study results now help accelerate efforts to better understand smell loss in patients with COVID-19, which could in turn lead to treatments for anosmia and the development of improved smell-based diagnostics for the disease.
"Anosmia seems like a curious phenomenon, but it can be devastating for the small fraction of people in whom it's persistent," Datta said. "It can have serious psychological consequences and could be a major public health problem if we have a growing population with permanent loss of smell."
The team also hope the data can help pave inroads for questions on disease progression such as whether the nose acts as a reservoir for SARS-CoV-2. Such efforts will require studies in facilities that allow experiments with live coronavirus and analyses of human autopsy data, the authors said, which are still difficult to come by. However, the collaborative spirit of pandemic-era scientific research calls for optimism.
"We initiated this work because my lab had a couple of datasets ready to analyze when the pandemic hit, and we published an initial preprint," Datta said. "What happened after that was amazing, researchers across the globe offered to share and merge their data with us in a kind of impromptu global consortium. This was a real collaborative achievement."
https://www.sciencedaily.com/releases/2020/07/200724141027.htm
Health, well-being and food security of families deteriorating under COVID-19 stress
July 24, 2020
Science Daily/Vanderbilt University Medical Center
The ongoing disruptive changes from efforts to reduce the spread of COVID-19 are having a substantial negative impact on the physical and mental well-being of parents and their children across the country, according to a new national survey published today in Pediatrics.
Families are particularly affected by stressors stemming from changes in work, school and day care schedules that are impacting finances and access to community support networks, according to the five-day survey of parents across the U.S. run June 5-June 10 run by Monroe Carell Jr. Children's Hospital at Vanderbilt and Ann & Robert H. Lurie Children's Hospital of Chicago.
Top line results showed:
27% of parents reported worsening mental health for themselves
14% reported worsening behavioral health for their children
24% of parents reported a loss of regular child care
The impact of abrupt, systemic changes to employment and strain from having access to a limited social network is disrupting the core of families across the country. Worsening physical and mental health were similar no matter the person's race, ethnicity, income, education status or location. However, larger declines in mental well-being were reported by women and unmarried parents.
"COVID-19 and measures to control its spread have had a substantial effect on the nation's children," said Stephen Patrick, MD, MPH, director of the Vanderbilt Center for Child Health Policy and a neonatologist at Children's Hospital in Nashville. "Today an increasing number of the nation's children are going hungry, losing insurance employer-sponsored insurance and their regular child care. The situation is urgent and requires immediate attention from federal and state policymakers."
Parents with children under age 18 were surveyed to measure changes in their health, insurance status, food security, use of public food assistance resources, child care and use of health care services since the COVID-19 pandemic began.
Since March, more families are reporting food insecurity, and more reliance on food banks, and delaying children's visits to health care providers. With COVID-19 cases and deaths on the rise around the country, families may continue to experience higher levels of need and disruption.
The proportion of families with moderate or severe food insecurity increased from 6% to 8% from March to June.
Children covered by parents' employer-sponsored insurance coverage decreased from 63% to 60%.
Strikingly, families with young children report worse mental health than those with older children, pointing to the central role that child care arrangements play in the day-to-day functioning of the family.
"The loss of regular child care related to COVID-19 has been a major shock to many families," says Matthew M. Davis, MD, MAPP, interim chair of the Department of Pediatrics at Northwestern University Feinberg School of Medicine and senior vice-president and chief of Community Health Transformation at Ann & Robert H. Lurie Children's Hospital of Chicago. "In almost half of all cases where parents said that their own mental health had worsened and that their children's behavior had worsened during the pandemic, they had lost their usual child care arrangements. We need to be aware of these types of stressors for families, which extend far beyond COVID-19 as an infection or an illness."
https://www.sciencedaily.com/releases/2020/07/200724104155.htm
Older adults feel stressed, yet resilient in the time of COVID-19
July 22, 2020
Science Daily/University of Georgia
America's oldest citizens say they've been through worse, but many older adults are feeling the stress of COVID-19 and prolonged social distancing measures, according to a new study from the University of Georgia.
And most are using a wider range of communication tools to stay in touch.
Study author Kerstin Emerson, a clinical associate professor of gerontology at UGA's Institute of Gerontology, said she's concerned that older adults could be experiencing more exacerbated feelings of loneliness due to social distancing.
"Many of the social venues that help older adults stay engaged are effectively cut off now with social distancing. While the internet can help with some connections, it is hard to replace human contact," said Emerson. "And for some these remote connections aren't possible due to no reliable internet."
Once states began issuing shelter-in-place orders, Emerson decided to conduct of survey of U.S. older adults to get an idea of how they were coping and some possible ways to help.
A total of 833 adults aged 60 and older living in the U.S. completed the survey between March 30 and April 12.
The Centers for Disease Control and Prevention released recommendations on March 5 encouraging older adults to stay home to protect themselves from COVID-19 exposure. By the time participants took the survey, they had been social distancing for an average of 17 days.
She was especially interested in how the responses differed among two subsets of survey participants -- those aged 60 to 70 and adults 71 and older.
"Part of the reason I did that was because I wanted to see if there was a difference by age groups, among the 'younger old' and 'older old,' who may have different work responsibilities and living situations," said Emerson.
Two themes emerged from survey responses, which seemed to break down along that age line. About 40% of 60- to 70-year-old respondents said they felt moderately or very stressed and felt out of control of their lives.
That could be why Emerson found that this subgroup reported more increases in some unhealthy behaviors, such as drinking more alcohol and eating more than usual. One-third report exercising less. Although Emerson also notes that one-third of the same group are exercising more.
But the older subgroup, those 71 and older, seem to be handling stress better than their younger counterparts -- 74% said that they were experiencing little to no stress, comparing the current situation to being no more stressful than living through past war times.
"That's where older adults have a strength," said Emerson. "They have life experience and coping mechanisms that we don't often give them credit for, but that's part of their wisdom. We can really turn to older adults as examples of how to manage and live through bad periods of history."
Unsurprisingly, communication across all modes has increased. More older adults are calling, texting, emailing and perusing social media.
Notably, compared to pre-social distancing, two-thirds of respondents are on social media, like Facebook, and using more smart devices. Over half reported using video calls once a day.
This information is key for public health practitioners, said Emerson, who are trying to craft interventions to support the emotional and physical well-being of older adults remotely.
Emerson noted that the survey respondents represent individuals who have access to the internet and a personal computer or smart device, "so we're probably not reaching the most vulnerable populations, people who are socially isolated in rural areas or who are incredibly poor."
There is always more to learn, said Emerson.
"The survey ends up raising more questions than giving answers in some cases, but that's the nature of it."
https://www.sciencedaily.com/releases/2020/07/200722163238.htm
Older adults coped with pandemic best
July 22, 2020
Science Daily/University of British Columbia
Adults aged 60 and up have fared better emotionally compared to younger adults (18-39) and middle-aged adults (40-59) amid the COVID-19 pandemic, according to new UBC research published recently in the Journal of Gerontology: Psychological Sciences.
Based on daily diary data collected between mid-March and mid-April of this year, the researchers found that older adults experienced greater emotional well-being and felt less stressed and threatened by the pandemic.
"Our findings provide new evidence that older adults are emotionally resilient despite public discourse often portraying their vulnerability. We also found that younger adults are at greater risk for loneliness and psychological distress during the pandemic," says Patrick Klaiber, the study's lead author and a graduate student in the UBC department of psychology.
For the study, the researchers analyzed data from 776 participants aged 18-91, who lived in Canada and the U.S. and completed daily surveys for one week about their stressors, positive events and their emotional well-being during the first several weeks of the pandemic. The time period was selected as it was likely to be the period of greatest disruption and uncertainty as local, provincial and state governments began issuing stay-at-home orders.
Klaiber says the difference in reported stress levels may be a result of age-related stressors and how well the different age groups respond to stress.
"Younger and middle-aged adults are faced with family- and work-related challenges, such as working from home, homeschooling children and unemployment," says Klaiber. "They are also more likely to experience different types of ongoing non-pandemic stressors than older adults, such as interpersonal conflicts."
Klaiber adds, "While older adults are faced with stressors such as higher rates of disease contraction, severe complications and mortality from COVID-19, they also possess more coping skills to deal with stress as they are older and wiser."
The study also reveals older and middle-aged adults experienced more daily positive events -- such as remote positive social interactions -- in 75 per cent of their daily surveys, which helped increase positive emotions compared to younger adults.
"While positive events led to increases in positive emotions for all three age groups, younger adults had the least positive events but also benefited the most from them," says Klaiber. "This is a good reminder for younger adults to create more opportunities for physically-distanced or remote positive experiences as a way of mitigating distress during the pandemic."
The researchers hope their findings would help inform the development of programs and strategies to bolster mental health for adults of all age groups.
https://www.sciencedaily.com/releases/2020/07/200722163229.htm
Study suggests increased risks for COVID-19 patients who smoke, vape
Researchers look for links between virus and stroke
July 22, 2020
Science Daily/Texas Tech University Health Sciences Center
As the SARS-CoV-2 virus, or COVID-19 has unfurled its tentacles across the globe, the severe respiratory and pulmonary disorders associated with the infection have become well known. However, recent case studies also have strongly suggested the presence of cerebrovascular-neurological dysfunction in COVID-19 patients, including large artery ischemic strokes that originate in one of the brain's larger blood-supplying arteries such as the carotid.
Luca Cucullo, Ph.D., and other researchers from the Texas Tech University Health Sciences Center (TTUHSC) have for years studied the effects smoking and vaping have on the cerebrovascular and neurological systems. Their research, and that of others, has shown smokers of tobacco and vaping products are more vulnerable to viral and bacterial infection than are non-smokers.
Based on those findings and the recent COVID-19 patient case studies, Cucullo and TTUHSC graduate research assistant Sabrina Rahman Archie reviewed the role smoking and vaping may play in the cerebrovascular and neurological dysfunction of those who contract the virus. Their study, "Cerebrovascular and Neurological Dysfunction under the Threat of COVID-19: Is There a Comorbid Role for Smoking and Vaping?" was published May 30 in the International Journal of Molecular Sciences.
In his previous research, Cucullo demonstrated how tobacco smoke can impair a person's respiratory function. From there, it can affect the vascular system and eventually the brain. Because COVID-19 also attacks the respiratory and vascular systems, he and Archie wanted to see if there were any reported cases indicating the virus may also affect the brain and lead to the onset of long-term neurological disorders like ischemic strokes. They also looked for evidence showing smoking and vaping can otherwise worsen the outcomes for COVID-19 patients, which Cucullo said seems to be the case.
Archie said some case studies demonstrate there are indeed stroke occurrences in COVID-19 patients and the rates appear to be increasing every day. In fact, one study of 214 patients found that 36.45% of COVID patients had neurological symptoms, further indicating the virus is able to affect the cerebral vascular system. But how does this happen?
There are within the human body approximately 13 blood coagulation factors that can be increased due to hypoxia, a condition that occurs when the body is deprived of sufficient amounts of oxygen at the tissue level, as occurs with smoking. Archie said COVID-19 appears to also raise some blood procoagulant, especially the von Wellebrand Factor, a blood clotting protein that primarily binds carries coagulation factor VIII and promotes platelet adhesion at the site of wounds.
"When the coagulant factor will be increased in our body, there will be a higher chance of clot formation," Archie explained. "Ultimately, it will be responsible for several vascular dysfunctions, for example, hemorrhagic or ischemic stroke."
Because COVID-19 and smoking or vaping each increases blood coagulation factors that may eventually affect the cerebral vascular system, Cucullo believes the stroke risk may be higher still for COVID-19 patients who smoke.
"COVID-19 seems to have this ability to increase the risk for blood coagulation, as does smoke," Cucullo added. "This may ultimately translate in higher risk for stroke."
Recent clinical study data also shows some of the damage caused by COVID-19, especially to the respiratory system, is permanent. Cucullo said the same data indicates that patients who recover from COVID-19 still have an elevated risk for stroke and that age and physical activity don't seem to be factors. Some of those with the highest risk factors for long-term problems related to COVID-19 are young adults in their 20s and 30s who were active and considered to be in their physical prime.
"After COVID-19, some of those can barely take few steps without having breathing issues, so the recovery, it's kind of formal recovering, but some of these long-term effects remain," he added.
In addition to impairing the immune and vascular systems and triggering cerebrovascular and neurological dysfunction, smoking and vaping often worsen the outcomes for patients who contract influenza or other respiratory or pulmonary diseases. Because COVID-19 appears to affect many of the same systems within the body, Cucullo said it would seem logical to think the health risks are increased for COVID-19 patients who smoke, but the virus is too new to know for certain.
"We don't even know whether COVID-19 can get into the brain because nobody has actually checked for it yet," Cucullo said. "I think it's very early for this kind of study; the prime clinical concern is either a vaccine or trying to alleviate the symptoms, in particular the respiratory symptoms, so they didn't even get that far. We are planning to do something from that point of view; this is something we will definitely research."
https://www.sciencedaily.com/releases/2020/07/200722083754.htm
Low level alcohol use during pregnancy can impact child's brain development
September 25, 2020
Science Daily/University of Sydney
New research from the University of Sydney finds that even low levels of alcohol consumption during pregnancy can have an impact on a child's brain development and is associated with greater psychological and behavioural problems in youth including anxiety, depression and poor attention.
Published today in the American Journal of Psychiatry, the study was led by the University's Matilda Centre for Research in Mental Health and Substance Use.
The impact of low-level alcohol use during pregnancy on child development is relatively unknown and there has been extensive debate about whether there is a safe level of consumption.
The researchers investigated whether any alcohol consumption in pregnancy was related to psychological, behavioural, neural and cognitive differences in children aged nine to ten years. With a sample of 9,719 youth, this is the largest study to investigate the impacts of low-level alcohol use during pregnancy. Low levels of drinking were considered one to two drinks per occasion with maximum of six drinks per week.
"Our research found that even small amounts of alcohol consumed while pregnant can have a significant impact on a child's brain development," said lead author Ms Briana Lees, PhD candidate at the Matilda Centre.
"Previous research has shown that very heavy alcohol use, such as binge drinking, during pregnancy can cause harm to the baby. However, this study shows that any alcohol use during pregnancy, even low levels, is associated with subtle, yet significant behavioural and psychological effects in children including anxiety, depression and poor attention.
"This study is so important because in Australia, around 50 percent of women drink alcohol before they know they are pregnant, and 25 percent do so after they know. The vast majority consume one or two standard drinks per occasion which this study shows is enough to impact the baby's brain."
Study findings
In the study, 25 percent of children had been exposed to alcohol in utero (in the womb), 60 percent of these children had been exposed to low-level alcohol use, and 40 per cent had been exposed to heavier levels. Heavier exposure being three or more drinks per occasion or seven or more drinks per week.
Children who were exposed to low levels of alcohol in-utero at any time during pregnancy experienced more psychological/emotional problems (including anxiety, depression and being withdrawn) and behavioural problems (including poor attention and being impulsive) than unexposed children. There was a 25 percent increased likelihood of an attention deficit hyperactivity disorder (ADHD) diagnosis in children who were exposed to slightly heavier levels of alcohol (approximately 36 drinks) in the first 6-7 weeks of pregnancy. Heavier alcohol use during early pregnancy was also associated with rule breaking behaviour and aggression, with a 30 percent higher risk of the child being diagnosed with oppositional defiant disorder than unexposed youth.
There were differences observed in brain volume and surface area among the exposed children which contributed to the psychological and behavioural problems. The estimated number of drinks consumed during pregnancy ranged from 0-90 with the average being 27. The majority of drinks were consumed in the first 6-7 weeks prior to pregnancy knowledge.
"Generally, the more a child was exposed to alcohol in utero the more severe the outcomes were," said Ms Lees.
"Children experienced negative effects even if they were only exposed to low levels of alcohol during very early pregnancy (approximately 16 drinks in the first six to seven weeks) and then the mother stopped drinking. The difficulty is many women don't know they are pregnant at that early stage.
Senior author Professor Maree Teesson, Director of the Matilda Centre said these findings are important for families, clinicians and policy makers moving forward.
"This research highlights the importance for women to be aware of the effects that even low levels of drinking can have on the brain development of babies," she said.
"The safest option during pregnancy is to abstain from drinking any alcohol.
"This information is also important for women planning pregnancies. Even when planning pregnancy, it is safer to abstain from any drinking. Any alcohol consumption from conception throughout the entire pregnancy can impact the brain development of their baby."
https://www.sciencedaily.com/releases/2020/09/200925113422.htm
Berry good news: newly discovered compound from blueberries could treat inflammatory disorders
Scientists show how a polyphenolic compound derived from blueberry can treat inflammatory bowel disease
September 23, 2020
Science Daily/Tokyo University of Science
Inflammatory bowel disease (IBD), caused by chronic inflammation in the digestive tract linings, can be debilitating and life threatening. Therapeutic options include suppression of immune response, but treatments leading to complete cure of IBD are still not available. Recently, a team of researchers has discovered a polyphenolic compound derived from blueberry that shows remarkable immunosuppressive effects and can be useful in treating IBD.
Various plants and their products are known to contain "bioactive" ingredients that can alleviate human diseases. These "phytocompounds" often contain restorative biological properties such as anti-cancerous, antioxidant, and anti-inflammatory effects. Thus, understanding how they interact with the body can lead to potential treatment strategies against major immune disorders.
A team of researchers at Tokyo University of Science, led by Prof Chiharu Nishiyama, has been working this direction for the past several years, to identify novel active components in functional foods and understand their effects on the body. Their efforts have now led to success: In their latest study, published in The FASEB Journal, the scientists identified a polyphenolic compound called "pterostilbene" (PSB) with strong immunosuppressive properties -- making it a potential therapeutic option for chronic inflammatory diseases, including inflammatory bowel disease (IBD). This compound is very similar to another phytocompound known to have important medicinal effects, called "resveratrol" (RSV). Dr Takuya Yashiro, corresponding author of this report, explains the idea that prompted their research, "RSV, a polyphenol, was known to have pronounced immunomodulatory and anti-inflammatory effects on animal models of colitis ulcer. Therefore, we investigated the possibility of other compounds structurally similar to RSV as a new type of treatment for IBD."
In patients with IBD, the gastrointestinal tract lining contains long-lasting ulcers caused by chronic inflammation due to an elevated immune response in the body. This involves the excessive production of immune system-related molecules called "cytokines." Moreover, two types of immune cells, "dendritic cells" (DCs) and "T cells," are also involved: at the onset of an immune response, DCs produce inflammatory cytokines and activate T cells to initiate a defense response. These processes together form a complex pathway that result in a "hyper" immune response. Thus, to find an effective compound that can suppress the immune system, it was crucial to test it on this population of immune cells.
Thus, to begin with, the scientists studied the effects of a range of plant-derived compounds on DC-mediated T cell proliferation. Their initial research led them to PSB, which showed stronger immunosuppressive activity than the other candidates. When they dug deeper, they found that PSB treatment prevents T cells from differentiating into Th1 and Th17 (subtypes of T cells that elevate the immune response) while increasing their differentiation into regulatory T cells (another subtype known to inhibit inflammation). They also revealed that PSB treatment inhibits inflammatory cytokine production from DCs by attenuating the DNA-binding activity of a crucial transcription factor PU.1. When they further tested PSB in mice with IBD, they found that oral intake of PSB improved symptoms of IBD. Thus, the study confirmed that PSB is an extremely promising anti-inflammatory agent to fight IBD. Not just this -- it is easily absorbed by the body, making it an ideal drug candidate!
Through these findings, the scientists have ushered in new possibilities for the treatment of not just IBD but also other inflammatory disorders. Dr Yashiro concludes, "For disease prevention, it is important to identify the beneficial components in foods and to understand the underlying mechanism by which immune responses and homeostasis are modulated in body. Our findings showed that PSB possesses a strong immunosuppressive property, paving the way for a new, natural treatment for IBD."
https://www.sciencedaily.com/releases/2020/09/200923164607.htm
Having high cholesterol levels early in life leads to heart problems by middle age
Finding could lead to more aggressive strategies to lower cholesterol in early adulthood
September 22, 2020
Science Daily/University of Maryland School of Medicine
Having elevated cholesterol during the teens or early twenties increases a person's risk of having a heart attack, stroke or other cardiovascular event during middle age. That is the finding a new landmark study led by researchers at the University of Maryland School of Medicine (UMSOM). This increased risk persists even in those who were able to get their cholesterol levels down to a healthy level before reaching their late thirties. The research makes a strong case for doctors to intervene early to treat high levels of low-density lipoprotein (LDL), the so-called "bad" type of cholesterol, the study authors contend. It also provides guidance for future intervention studies aimed at stemming the worldwide epidemic of heart disease and stroke.
The study, entitled "Time Course of LDL Cholesterol Exposure and Cardiovascular Disease Event Risk," was published today in the Journal of the American College of Cardiology and relied on data from the Coronary Artery Risk Development in Young Adults Study (CARDIA). This ongoing study, funded by the National Heart, Lung, and Blood Institute, began 35 years ago, recruiting 5,000 young adults aged 18 to 30. It has been tracking this cohort ever since to understand how individual characteristics, lifestyle and environmental factors contribute to the development of cardiovascular disease later in life.
"We found having an elevated LDL cholesterol level at a young age raises the risk of developing heart disease, and the elevated risk persists even in those who were able to later lower their LDL cholesterol levels" said study leader Michael Domanski, MD, a Professor of Medicine at UMSOM. For instance, two people with the same cholesterol level at age 40 may have very different risks of having a heart attack or stroke with risk being higher for the person who had higher cholesterol as a teenager.
"Damage to the arteries done early in life may be irreversible and appears to be cumulative," Dr. Domanski said. "For this reason, doctors may want to consider prescribing lifestyle changes and also medications to lower high LDL cholesterol levels in young adults in order to prevent problems further down the road."
To conduct the study, the researchers used complex mathematical modeling to understand how cardiovascular risk (heart attack, stroke, blood vessel blockages, and death from cardiovascular disease) rises with increasing cumulative "exposure" to LDL cholesterol over an average of 22 years. They found that the greater the area under the "LDL curve" -- which measured time of exposure and level of LDL cholesterol over time -- the more likely participants were to experience a major cardiovascular event.
"Interestingly and importantly, we also found it was not just the area under the curve that accounted for the difference in risk but also the time course of the exposure," study co-author Charles Hong, MD, PhD, the Melvin Sharoky, MD, Professor in Medicine at UMSOM. "This underscores the importance of regular cholesterol screenings beginning in early adulthood to help reduce this time of high exposure."
While the medical establishment understands the importance of managing high LDL cholesterol levels to lower heart risks, there is little consensus on how aggressively to intervene in young adults who may not experience a heart attack or stroke for decades. The American College of Cardiology's current cholesterol management guidelines recommend using lifestyle measures to lower high LDL levels during the teenage years. This includes exercise, maintaining a healthy body mass index, and following a healthy diet low in saturated animal fats. The guidelines recommend that doctors consider prescribing cholesterol-lowering medications like statins to prevent heart disease in those ages 20 to 39 who have elevated cholesterol levels, especially if they have a family history of early-onset heart disease.
Researchers from the National Heart, Lung, and Blood Institute, George Washington University, Northwestern Feinberg School of Medicine, University of Alabama School of Medicine, the University of Toronto and the Icahn School of Medicine at Mount Sinai were co-authors on this study.
"Cardiovascular disease remains the biggest killer in the world, and this new finding provides a potential way to save many lives," said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "The medical community should sit up, take notice, and respond to this important new evidence."
https://www.sciencedaily.com/releases/2020/09/200922172604.htm
Fatter legs linked to reduced risk of high blood pressure
September 10, 2020
Science Daily/American Heart Association
Adults with fatter legs -- meaning they have a higher percentage of total body fat tissue in their legs -- were less likely than those with a lower percentage to have high blood pressure, according to new research to be presented Sept. 10-13, 2020, at the virtual American Heart Association's Hypertension 2020 Scientific Sessions. The meeting is a premier global exchange for clinical and basic researchers focusing on recent advances in hypertension research.
"Ultimately, what we noted in this study is a continued discussion of 'it's not just how much fat you have, but where the fat is located,'" said principal investigator Aayush Visaria, M.P.H., a fourth-year medical student at Rutgers New Jersey Medical School in Newark, New Jersey. "Although we know confidently that fat around your waist is detrimental to health, the same cannot be said for leg fat. If you have fat around your legs, it is more than likely not a bad thing and may even be protecting you from hypertension, according to our findings."
The investigators examined the rate of three types of high blood pressure in relation to the percentage of fat tissue in the legs of nearly 6,000 adults enrolled in the 2011-2016 National Health & Nutrition Examination Surveys. Average age of the participants was 37, nearly half were female and 24% had high blood pressure, defined as blood pressure >130/80 mm Hg.
Special X-ray scans measured fat tissue in the legs, and these measures were compared to overall body fat tissue. Investigators classified participants as having either a high or low percentage of leg fat, with high fat defined as 34% or more for males, and 39% or more for females.
Participants with higher percentages of leg fat were less likely than those with lower levels of fat to have all types of high blood pressure. The analysis found:
Compared to those with lower percentages of leg fat, participants with higher percentages of leg fat were 61% less likely to have the type of high blood pressure where both numbers are elevated.
In addition, risk for participants with higher leg fat was 53% lower for diastolic high blood pressure (the second number in a blood pressure reading, measuring pressure between heart beats) and 39% lower for systolic high blood pressure (the first number in a reading, measuring pressure when the heart beats).
After adjusting for various factors, such as age, sex, race and ethnicity, education, smoking, alcohol use, cholesterol levels and waist fat, the risk for high blood pressure was still lower among participants with higher percentages of leg fat, although not as low as before adjusting for these factors.
"If these results are confirmed by larger, more robust studies, and in studies using easily accessible measurement methods like thigh circumference, there is the potential to affect patient care," Visaria said. "Just as waist circumference is used to estimate abdominal fat, thigh circumference may be a useful tool, although it's a bit cumbersome and not as widely studied in the U.S. population."
Several limitations could have affected the study's results. First, the study could not determine cause and effect, since information on blood pressure and percentage of fat tissue in the legs were measured at the same time. Second, a larger group of participants is needed to yield more information about the effects on high blood pressure of varying degrees of fat tissue in the legs. Finally, all study participants were under the age of 60, so the results may not apply to older adults, who are generally at greater risk for high blood pressure.
https://www.sciencedaily.com/releases/2020/09/200910150338.htm
Gut microbiome data may be helpful in routine screening of cardiovascular disease
September 10, 2020
Science Daily/American Heart Association
Previous studies have found the human gut microbiome, bacteria in the gastrointestinal tract, is associated with cardiovascular disease (CVD). This study used machine learning to analyze data from nearly 1,000 stool samples from people with and without CVD. Results show potential for developing a convenient, new diagnostic approach for CVD.
Using artificial intelligence to analyze the bacteria in a person's gut microbiome shows promise as a new screening method for cardiovascular disease (CVD), according to preliminary research to be presented Sept. 10-13, 2020, at the virtual American Heart Association's Hypertension 2020 Scientific Sessions. The meeting is a premier global exchange for clinical and basic researchers focusing on recent advances in hypertension research. The full study published simultaneously today in Hypertension, an American Heart Association journal.
Recent studies have found a link between gut microbiota, the microorganisms in human digestive tracts, and CVD, which is the leading cause of mortality worldwide. Gut microbiota is highly variable between individuals, and differences in gut microbial compositions between people with and without CVD have been reported.
"Based on our previous research linking gut microbiota to CVD in animal models, we designed this study to test whether it is possible to screen for CVD in humans using artificial intelligence screening of stool samples," said Bina Joe, Ph.D., FAHA, the study director, Distinguished University Professor and Chairwoman of the department of physiology and pharmacology at the University of Toledo in Toledo, Ohio. "Gut microbiota has a profound effect on cardiovascular function, and this could be a potential new strategy for evaluation of cardiovascular health."
Researchers used data from the American Gut Project (an open platform for microbiome research based in the United States) to analyze microbial composition of stool samples with state-of-the-art machine learning modeling. Nearly 1,000 samples were analyzed, and approximately half of the samples were from people with CVD. The model was able to identify different clusters of gut bacteria that could potentially help identify individuals with existing CVD and without CVD.
Among the bacteria identified:
Bacteroides, Subdoligranulum, Clostridium, Megasphaera, Eubacterium, Veillonella, Acidaminococcus and Listeria were more abundant in the CVD group.
Faecalibacterium, Ruminococcus, Proteus, Lachnospira, Brevundimonas, Alistipes and Neisseria were more abundant in the non-CVD group.
"Despite the fact that gut microbiomes are highly variable among individuals, we were surprised by the promising level of accuracy obtained from these preliminary results, which indicate fecal microbiota composition could potentially serve as a convenient diagnostic screening method for CVD," Joe said. "It is conceivable that one day, maybe without even assessing detailed cardiovascular function, clinicians could analyze the gut microbiome of patients' stool samples with an artificial machine learning method to screen patients for heart and vascular diseases."
https://www.sciencedaily.com/releases/2020/09/200910150336.htm
Women's heart health linked to age at first menstrual period
New study suggests that early menarche is associated with worse cardiovascular health, especially in young women
September 9, 2020
Science Daily/The North American Menopause Society (NAMS)Early menarche has been associated with many cardiovascular disease (CVD) risk factors, but little is known about its association with overall heart health. One new study suggests that age at menarche plays an important role in maintaining and improving cardiovascular health, although there are a number of age differences. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).
Because CVD is the leading cause of death in women, a lot of research is devoted to identifying ways for women to improve their heart health and prevent major cardiovascular events. Cardiovascular health takes into account factors such as blood pressure, total cholesterol, and glucose levels, as well as behavioral factors including cigarette smoking, body mass index, physical activity, and diet. Ideal cardiovascular health is associated with a lower risk of CVD, as well as with other outcomes such as cancer, cognitive impairment, and depression. Studies have shown that ideal cardiovascular health is prevalent in 50% of the US population at 10 years of age and declines to less than 10% by 50 years of age.
Some forms of CVD have their origins during childhood, which is one reason why they have been previously associated with early menarche. To date, however, few if any studies have focused on the association between early menarche (generally defined as the occurrence of first menstruation before 12 years of age) and overall cardiovascular health. This new study involving more than 20,000 women not only found that increases in age at menarche are significantly associated with increases in heart health in women but also that there are major age differences in the association. In fact, significant associations between age at menarche and ideal cardiovascular health were observed only in young women, whereas little association was documented in older women. This suggests that age at menarche may be less of a predictor of heart health as women age.
Similarly, the researchers found that the protective effects of late menarche on cardiovascular health were apparent in women aged 25 to 44 years, whereas the detrimental effects of early menarche were only observed in those aged 25 to 34 years. Further studies are necessary to better understand the reason behind these declining associations.
Results are published in the article "Age at menarche and cardiovascular health: results from the NHANES 1999-2016."
"This study highlights a link between age at menarche and cardiovascular health, findings that were evident only in younger women and may be driven by associations with body mass index. Given that heart disease is the number one killer of women, identifying those women who experienced early menarche (aged younger than 12 years) may allow for earlier intervention to reduce cardiovascular risk," says Dr. Stephanie Faubion, NAMS medical director.
https://www.sciencedaily.com/releases/2020/09/200909114812.htm
Healthy diet and exercise during pregnancy could lead to healthier children
September 11, 2020
Science Daily/King's College London
New research shows improving the lifestyle of women with obesity during pregnancy could mean long-term cardiovascular benefits for their children.
The study, led by King's College London and supported by the British Heart Foundation and Tommy's charity, examined how an antenatal diet and physical activity intervention in pregnant women with obesity could positively influence the health of the women and their children three years after giving birth.
The UPBEAT trial is a randomised controlled trial which aims to improve the diet and physical activity of obese pregnant women across the UK. Women who were given a diet and exercise intervention were compared to women in a control group, who made no changes to their lifestyle during pregnancy.
Follow-up examinations three years after birth showed that the children born to the intervention arm of the trial had a lower resting heart rate of -5 bpm than children treated with standard care. A higher resting heart rate in adults is associated with hypertension and cardiovascular dysfunction.
The study also showed that mothers in the intervention arm maintained a healthier diet three years after birth.
While women reported lower glycaemic load, maternal energy and saturated fatty acids intake, and higher protein intake three years after delivery, there were no differences in self-reported physical activity or in measures of body composition.
Lead author Kathryn Dalrymple from King's College London said: "This research shows that an lifestyle intervention in pregnant women, which focused on improving diet and increasing physical activity, is associated with improved cardiovascular function in the child at three-years of age and a sustained improvement in the mothers diet, three years after the intervention finished. These findings are very exciting as they add to the evidence that pregnancy is a window of opportunity to promote positive health and lifestyle changes which benefit the mother and her child."
Senior author Professor Lucilla Poston, Tommy's Chair for Maternal and Fetal Health, said: "Obesity in pregnancy is a major problem because it can increase the risk of complications in pregnancy as well as affecting the longer-term health of the child. This study strengthens my resolve to highlight just how important it is that we give children a healthy start in life."
Tommy's Research and Policy Director, Lizzie D'Angelo, said: "Pregnancy can be higher risk for women who are obese, but trying to lose lots of weight while pregnant is not advised, so our research focuses on finding new ways to make pregnancy safer for these families. It's very reassuring to see that our researchers have been able to improve mothers' diets and children's heart health in the long term, helping to give these babies the best start in life."
Tracy Parker, Senior Dietitian at the British Heart Foundation, said: "Keeping physically active and maintaining a balanced diet are both important ways of keeping our hearts healthy. This research shows that for pregnant women, the benefits don't end there. A healthy diet before, during and after pregnancy can have positive long-term health benefits for both mother and child."
The team of researchers will follow-up these children again at 8-10 years of age to see if this improvement in cardiovascular function is maintained through childhood.
https://www.sciencedaily.com/releases/2020/09/200911110804.htm