COVID-19: Study shows virus can infect heart cells in lab dish

Research uses stem cell technology to learn how coronavirus may directly attack heart muscle

June 30, 2020

Science Daily/Cedars-Sinai Medical Center

A new study shows that SARS-CoV-2, the virus that causes COVID-19 (coronavirus), can infect heart cells in a lab dish, indicating it may be possible for heart cells in COVID-19 patients to be directly infected by the virus. The discovery, published today in the journal Cell Reports Medicine, was made using heart muscle cells that were produced by stem cell technology.

Although many COVID-19 patients experience heart problems, the reasons are not entirely clear. Pre-existing cardiac conditions or inflammation and oxygen deprivation that result from the infection have all been implicated. But until now, there has been only limited evidence that the SARS-CoV-2 virus directly infects the individual muscle cells of the heart.

"We not only uncovered that these stem cell-derived heart cells are susceptible to infection by novel coronavirus, but that the virus can also quickly divide within the heart muscle cells," said Arun Sharma, PhD, a research fellow at the Cedars-Sinai Board of Governors Regenerative Medicine Institute and first and co-corresponding author of the study. "Even more significant, the infected heart cells showed changes in their ability to beat after 72 hours of infection."

The study also demonstrated that human stem cell-derived heart cells infected by SARS-CoV-2 change their gene expression profile, further confirming that the cells can be actively infected by the virus and activate innate cellular "defense mechanisms" in an effort to help clear out the virus.

While these findings are not a perfect replicate of what is happening in the human body, this knowledge may help investigators use stem cell-derived heart cells as a screening platform to identify new antiviral compounds that could alleviate viral infection of the heart, according to senior and co-corresponding author Clive Svendsen, PhD.

"This viral pandemic is predominately defined by respiratory symptoms, but there are also cardiac complications, including arrhythmias, heart failure and viral myocarditis," said Svendsen, director of the Regenerative Medicine Institute and professor of Biomedical Sciences and Medicine. "While this could be the result of massive inflammation in response to the virus, our data suggest that the heart could also be directly affected by the virus in COVID-19."

Researchers also found that treatment with an ACE2 antibody was able to blunt viral replication on stem cell-derived heart cells, suggesting that the ACE2 receptor could be used by SARS-CoV-2 to enter human heart muscle cells.

"By blocking the ACE2 protein with an antibody, the virus is not as easily able to bind to the ACE2 protein, and thus cannot easily enter the cell," said Sharma. "This not only helps us understand the mechanisms of how this virus functions, but also suggests therapeutic approaches that could be used as a potential treatment for SARS-CoV-2 infection."

The study used human induced pluripotent stem cells (iPSCs), a type of stem cell that is created in the lab from a person's blood or skin cells. IPSCs can make any cell type found in the body, each one carrying the DNA of the individual. Tissue-specific cells created in this way are used for research and for creating and testing potential disease treatments.

"This work illustrates the power of being able to study human tissue in a dish," said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute, who collaborated with Sharma and Svendsen on the study. "It is plausible that direct infection of cardiac muscle cells may contribute to COVID-related heart disease."

The investigators also collaborated with co-corresponding author Vaithilingaraja Arumugaswami, DVM, PhD, an associate professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. Arumugaswami provided the novel coronavirus that was added to the heart cells, and UCLA researcher Gustavo Garcia Jr. contributed essential heart cell infection experiments.

"This key experimental system could be useful to understand the differences in disease processes of related coronaviral pathogens, SARS and MERS," Arumugaswami said.

https://www.sciencedaily.com/releases/2020/06/200630155745.htm

 

Lab-grown 'mini-brains' suggest COVID-19 virus can infect human brain cells

June 30, 2020

Science Daily/Johns Hopkins Medicine

A multidisciplinary team from two Johns Hopkins University institutions, including neurotoxicologists and virologists from the Bloomberg School of Public Health and infectious disease specialists from the school of medicine, has found that organoids (tiny tissue cultures made from human cells that simulate whole organs) known as "mini-brains" can be infected by the SARS-CoV-2 virus that causes COVID-19.

The results, which suggest that the virus can infect human brain cells, were published online June 26, 2020, in the journal ALTEX: Alternatives to Animal Experimentation.

Early reports from Wuhan, China, the origin of the COVID-19 pandemic, have suggested that 36% of patients with the disease show neurological symptoms, but it has been unclear whether or not the virus infects human brain cells. In their study, the Johns Hopkins researchers demonstrated that certain human neurons express a receptor, ACE2, which is the same one that the SARS-CoV-2 virus uses to enter the lungs. Therefore, they surmised, ACE2 also might provide access to the brain.

When the researchers introduced SARS-CoV-2 virus particles into a human mini-brain model, the team found -- for what is believed to be the first time -- evidence of infection by and replication of the pathogen.

The human brain is well-shielded against many viruses, bacteria and chemical agents by the blood-brain barrier, which in turn, often prevents infections of the brain. "Whether or not the SARS-CoV-2 virus passes this barrier has yet to be shown," notes senior author Thomas Hartung, M.D., Ph.D., chair for evidence-based toxicology at the Bloomberg School of Public Health. "However, it is known that severe inflammations, such as those observed in COVID-19 patients, make the barrier disintegrate."

The impermeability of the blood-brain barrier, he adds, also can present a problem for drug developers targeting the brain.

The impact of SARS-CoV-2 on the developing brain is another concern raised by the study. Previous research from Paris-Saclay University has shown that the virus crosses the placenta, and embryos lack the blood-brain barrier during early development. "To be very clear," Hartung says, "we have no evidence that the virus produces developmental disorders."

However, the mini-brains -- which model the growing human brain -- contain the ACE2 receptor from their earliest stages of development. Therefore, Hartung says, the findings suggest that extra caution should be taken during pregnancy.

"This study is another important step in our understanding of how infection leads to symptoms, and where we might tackle the COVID-19 disease with drug treatment," says William Bishai, M.D., Ph.D., professor of medicine at the Johns Hopkins University School of Medicine, and leader of the infectious disease team for the study.

The human stem cell-derived mini-brain models -- known as BrainSpheres -- were developed at the Bloomberg School of Public Health four years ago. They were the first mass-produced, highly standardized organoids of their kind, and have been used to model a number of diseases, including infections by viruses such as Zika, dengue and HIV.

https://www.sciencedaily.com/releases/2020/06/200630111445.htm

Life-hack: Rituals spell anxiety relief

June 30, 2020

Science Daily/University of Connecticut

With graduation ceremonies, weddings, funeral, annual parades, and many other gatherings called off, it is apparent that our lives are filled with rituals. UConn Assistant Professor of Anthropology Dimitris Xygalatas studies rituals and how they impact our health. In research published today in Philosophical Transactions of the Royal Society, Xygalatas and collaborators from Masaryk University, Czech Republic, including former UConn student Martin Lang, examine the important roles rituals play in reducing our anxiety levels.

"In the current context of the pandemic, if you were a completely rational being -- perhaps an extraterrestrial who's never met any actual humans -- you would expect that given the current situation people wouldn't bother doing things that do not seem crucial to their survival. Maybe they wouldn't care so much about art, sports, or ritual, and they would focus on other things," says Xygalatas. "If you were to think that, it would show you didn't know much about human nature, because humans care deeply about those things."

Further, Xygalatas says, rituals play an important role in people's lives, helping them cope with anxiety and functioning as mechanisms of resilience.

This research started years ago, says Xygalatas. He explains that to study something as complex as human behavior, it is important to approach the question from multiple angles to collect converging evidence. First, in a laboratory study, they found that inducing anxiety made people's behavior more ritualized, that is, more repetitive and structured. So the next step was to take this research out to real-life situations, where they examined whether performing cultural rituals in their natural context indeed helps practitioners cope with anxiety.

"This approach also goes to show the limitations of any study. One study can only tell us a tiny bit about anything, but by using a variety of methods like my team and I are doing, and by going between the highly controlled space of the lab and the culturally relevant place that is real life we are able to get a more holistic perspective."

The experiment reported in their current publication took place in Mauritius, where the researchers induced anxiety by asking participants to prepare a plan for dealing with a natural disaster that would be evaluated by government experts. This was stressful, as floods and cyclones are very pertinent threats in that context. Following this stress-inducing task, one half of the group performed a familiar religious ritual at the local temple while the other half were asked to sit and relax in a non-religious space.

The researchers found that the speech was successful in inducing for both groups but those who performed the religious ritual experienced a greater reduction in both psychological and physiological stress, which was assessed by using wearable technology to measure heart rate variability.

Stress itself is important, says Xygalatas, "Stress acts as a motivation that helps us focus on our goals and rise to meet our challenges, whether those involve studying for an exam, flying a fighter jet, or scoring that game-winning goal. The problem is that beyond a certain threshold, stress ceases to be useful. In fact, it can even be dangerous. Over time, its effects can add up and take a toll on your health, impairing cognitive function, weakening the immune system, and leading to hypertension or cardiovascular disease. This type of stress can be devastating to our normal functioning, health, and well-being."

This is where Xygalatas and his team believe ritual plays an important role in managing stress.

"The mechanism that we think is operating here is that ritual helps reduce anxiety by providing the brain with a sense of structure, regularity, and predictability."

Xygalatas explains that in recent decades we have begun to realize the brain is not a passive computer but an active predictive machine, registering information and making predictions to help us survive.

"We come to expect certain things -- our brain fills in the missing information for the blind spot in our vision, and prompts us to anticipate the next word in a sentence -- all of these things are due to this effect because our brain makes active predictions about the state of the world."

Well-practiced rituals, like the one included in the study, are repetitive and predictable and therefore the researchers believe they give our brains the sense of control and structure that we crave, and those feelings help alleviate stress. This stress reducing impact of rituals could be a way to cope with chronic anxiety.

In today's stressful context, we see ritual taking different forms, from people gathering to applaud healthcare workers, to virtual choirs singing across the internet. Xygalatas also notes a recent study that tracked the increase in people typing 'prayer' in Google searches. In this unpredictable time, people are continuing to find relief in ritual.

"One thing I like to tell my students is that we as human beings are not as smart as we'd like to think. But thankfully, we are at least smart enough to be able to outsmart ourselves. We have many ways of doing this, for instance when we look at ourselves in the mirror before an interview and tell ourselves, 'Ok I can do this'. Or when we take deep breaths to calm down. We have all of these hacks that we can use on our very brain. We could rationalize it and tell ourselves 'Ok I'm going to lower my heartbeat now'. Well that doesn't work. Ritual is one of those mental technologies that we can use to trick ourselves into doing that. That is what these rituals do -- they act like life hacks for us."

Going forward, Xygalatas points out that he and his colleagues intend to do more work on the exact mechanisms underlying these effects of ritual.

"Of course it is a combination of factors, and that is why ritual is so powerful: because it combines a number of mechanisms that have to do both with the behavior itself, the physical movements, and with the cultural context, the symbolism, and the expectations that go into that behavior. To be able to disentangle those things is what we are trying to do next: we are examining these factors one at a time. Those rituals have gone through a process of cultural selection and they are still with us because they fulfil specific functions. They are life hacks that have been with and have served us well since the dawn of our kind."

https://www.sciencedaily.com/releases/2020/06/200630111504.htm

Seeing is believing: Effectiveness of facemasks

Researchers use flow visualization to qualitatively test facemasks and social distancing

June 30, 2020

Science Daily/Florida Atlantic University

Using flow visualization, researchers assessed the efficacy of facemasks in obstructing respiratory droplets. Loosely folded facemasks and bandana-style coverings provide minimal stopping-capability for the smallest aerosolized respiratory droplets. Well-fitted homemade masks with multiple layers of quilting fabric, and off-the-shelf cone style masks, proved to be the most effective in reducing droplet dispersal. Importantly, uncovered coughs were able to travel noticeably farther than the currently recommended 6-foot distancing guideline. Without a mask, droplets traveled more than 8 feet.

Currently, there are no specific guidelines on the most effective materials and designs for facemasks to minimize the spread of droplets from coughs or sneezes to mitigate the transmission of COVID-19. While there have been prior studies on how medical-grade masks perform, data on cloth-based coverings used by the vast majority of the general public are sparse.

Research from Florida Atlantic University's College of Engineering and Computer Science, just published in the journal Physics of Fluids, demonstrates through visualization of emulated coughs and sneezes, a method to assess the effectiveness of facemasks in obstructing droplets. The rationale behind the recommendation for using masks or other face coverings is to reduce the risk of cross-infection via the transmission of respiratory droplets from infected to healthy individuals.

Researchers employed flow visualization in a laboratory setting using a laser light sheet and a mixture of distilled water and glycerin to generate the synthetic fog that made up the content of a cough-jet. They visualized droplets expelled from a mannequin's mouth while simulating coughing and sneezing. They tested masks that are readily available to the general public, which do not draw away from the supply of medical-grade masks and respirators for healthcare workers. They tested a single-layer bandana-style covering, a homemade mask that was stitched using two-layers of cotton quilting fabric consisting of 70 threads per inch, and a non-sterile cone-style mask that is available in most pharmacies. By placing these various masks on the mannequin, they were able to map out the paths of droplets and demonstrate how differently they perform.

Results showed that loosely folded facemasks and bandana-style coverings provide minimal stopping-capability for the smallest aerosolized respiratory droplets. Well-fitted homemade masks with multiple layers of quilting fabric, and off-the-shelf cone style masks, proved to be the most effective in reducing droplet dispersal. These masks were able to curtail the speed and range of the respiratory jets significantly, albeit with some leakage through the mask material and from small gaps along the edges.

Importantly, uncovered emulated coughs were able to travel noticeably farther than the currently recommended 6-foot distancing guideline. Without a mask, droplets traveled more than 8 feet; with a bandana, they traveled 3 feet, 7 inches; with a folded cotton handkerchief, they traveled 1 foot, 3 inches; with the stitched quilted cotton mask, they traveled 2.5 inches; and with the cone-style mask, droplets traveled about 8 inches.

"In addition to providing an initial indication of the effectiveness of protective equipment, the visuals used in our study can help convey to the general public the rationale behind social-distancing guidelines and recommendations for using facemasks," said Siddhartha Verma, Ph.D., lead author and an assistant professor who co-authored the paper with Manhar Dhanak, Ph.D., department chair, professor, and director of SeaTech; and John Frakenfeld, technical paraprofessional, all within FAU's Department of Ocean and Mechanical Engineering. "Promoting widespread awareness of effective preventive measures is crucial at this time as we are observing significant spikes in cases of COVID-19 infections in many states, especially Florida."

When the mannequin was not fitted with a mask, they projected droplets much farther than the 6-foot distancing guidelines currently recommended by the United States Centers for Disease Control and Prevention. The researchers observed droplets traveling up to 12 feet within approximately 50 seconds. Moreover, the tracer droplets remained suspended midair for up to three minutes in the quiescent environment. These observations, in combination with other recent studies, suggest that current social-distancing guidelines may need to be updated to account for aerosol-based transmission of pathogens.

"We found that although the unobstructed turbulent jets were observed to travel up to 12 feet, a large majority of the ejected droplets fell to the ground by this point," said Dhanak. "Importantly, both the number and concentration of the droplets will decrease with increasing distance, which is the fundamental rationale behind social-distancing."

The pathogen responsible for COVID-19 is found primarily in respiratory droplets that are expelled by infected individuals during coughing, sneezing, or even talking and breathing. Apart from COVID-19, respiratory droplets also are the primary means of transmission for various other viral and bacterial illnesses, such as the common cold, influenza, tuberculosis, SARS (Severe Acute Respiratory Syndrome), and MERS (Middle East Respiratory Syndrome), to name a few. These pathogens are enveloped within respiratory droplets, which may land on healthy individuals and result in direct transmission, or on inanimate objects, which can lead to infection when a healthy individual comes in contact with them.

"Our researchers have demonstrated how masks are able to significantly curtail the speed and range of the respiratory droplets and jets. Moreover, they have uncovered how emulated coughs can travel noticeably farther than the currently recommended six-foot distancing guideline," said Stella Batalama, Ph.D., dean of FAU's College of Engineering and Computer Science. "Their research outlines the procedure for setting up simple visualization experiments using easily available materials, which may help healthcare professionals, medical researchers, and manufacturers in assessing the effectiveness of face masks and other personal protective equipment qualitatively."

https://www.sciencedaily.com/releases/2020/06/200630111449.htm

Whole-town study reveals more than 40% of COVID-19 infections had no symptoms

June 30, 2020

Science Daily/Imperial College London

A study of COVID-19 in the quarantined Italian town of Vò, where most of the population was tested, reveals the importance of asymptomatic cases.

The authors of the new research, from the University of Padova and at Imperial College London, published today in Nature, suggest asymptomatic or pre-symptomatic people are an important factor in the transmission of COVID-19. They also argue that widespread testing, isolating infected people, and a community lockdown effectively stopped the outbreak in its tracks.

The town of Vò, with a population of nearly 3,200 people, experienced Italy's first COVID-19 death on 21 February 2020. The town was put into immediate quarantine for 14 days. During this time, researchers tested most of the population for infection of SARS-CoV-2, the virus that causes COVID-19, both at the start of the lockdown (86 percent tested) and after two weeks (72 percent tested).

The testing revealed that at the start of the lockdown, 2.6 percent of the population (73 people) were positive for SARS-CoV-2, while after a couple of weeks only 1.2 percent (29 people) were positive. At both times, around 40 percent of the positive cases showed no symptoms (asymptomatic). The results also show it took on average 9.3 days (range of 8-14 days) for the virus to be cleared from someone's body.

None of the children under ten years old in the study tested positive for COVID-19, despite several living with infected family members. This is in contrast to adults living with infected people, who were very likely to test positive.

As a result of the mass testing any positive cases, symptomatic or not, were quarantined, slowing the spread of the disease and effectively suppressing it in only a few short weeks.

Co-lead researcher Professor Andrea Crisanti, from the Department of Molecular Medicine of the University of Padua and the Department of Life Sciences at Imperial, said: "Our research shows that testing of all citizens, whether or not they have symptoms, provides a way to manage the spread of disease and prevent outbreaks getting out of hand. Despite 'silent' and widespread transmission, the disease can be controlled."

The results of the mass testing programme in Vò informed policy in the wider Veneto Region, where all contacts of positive cases were offered testing. "This testing and tracing approach has had a tremendous impact on the course of the epidemic in Veneto compared to other Italian regions, and serves as a model for suppressing transmission and limiting the virus' substantial public health, economic and societal burden," added Professor Crisanti.

As well as identifying the proportion of asymptomatic cases, the team also found that asymptomatic people had a similar 'viral load' -- the total amount of virus a person has inside them -- as symptomatic patients.

Viral load also appeared to decrease in people who had no symptoms to begin with but later developed symptoms, suggesting that asymptomatic and pre-symptomatic transmission could contribute significantly to the spread of disease, making testing and isolating even more important in controlling outbreaks.

Co-lead researcher Dr Ilaria Dorigatti, from the MRC Centre for Global Infectious Disease Analysis, Jameel Institute (J-IDEA), at Imperial College London, said: "The Vò study demonstrates that the early identification of infection clusters and the timely isolation of symptomatic as well as asymptomatic infections can suppress transmission and curb an epidemic in its early phase. This is particularly relevant today, given the current risk of new infection clusters and of a second wave of transmission.

"There are still many open questions about the transmission of the SARS-CoV-2 virus, such as the role of children and the contribution of asymptomatic carriers to transmission. Finding answers to these questions is crucial to identifying targeted and sustainable control strategies to combat the spread of SARS-CoV-2 in Italy and around the world."

Professor Enrico Lavezzo, from the Department of Molecular Medicine at the University of Padua said: "The result concerning asymptomatic carriers is key. We took a picture of the Vò population and found that about half of the population testing positive had no symptoms at the time of testing and some of them developed symptoms in the following days. This tells us that if we find a certain number of symptomatic people testing positive, we expect the same number of asymptomatic carriers that are much more difficult to identify and isolate.

"The fact that the viral load is comparable between symptomatic and asymptomatic carriers means even asymptomatic infections have the potential to contribute to transmission, as some of the reconstructed chain of transmission obtained from the detailed contact tracing conducted in Vò confirmed.

"On the one hand, it is likely that a symptomatic infection transmits large quantities of virus, for example via coughing, but it is also reasonable to think that symptoms may induce a person with a symptomatic infection to stay at home, limiting the number of contacts and hence the transmission potential. On the other hand, someone with an asymptomatic infection is entirely unconscious of carrying the virus and, according to their lifestyle and occupation, could meet a large number of people without modifying their behaviour."

Co-first author Dr Elisa Franchin, from the Department of Molecular Medicine of the University of Padua, said: "This work highlights the efficacy of the containment strategies implemented since the finding of the first positive patient in the town of Vò. From a technical perspective, this work has been possible thanks to the most advanced diagnostic technologies that we had available and to the work of a large number of people with different skills: from nurses to clerks, technicians, biologists and medical doctors. The en mass participation of the Vo' population to this study has given us the opportunity to better understand the transmission of this virus and how to avoid future infections."

This research was funded by the Veneto Region, Wellcome Trust, Royal Society, the European Union's Horizon 2020 research and innovation programme, the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement, the EDCTP2 programme supported by the European Union and the Abdul Latif Jameel Foundation.

https://www.sciencedaily.com/releases/2020/06/200630103557.htm

Even in the worst COVID-19 cases, the body launches immune cells to fight back

International collaboration provides important piece of COVID-19 puzzle

June 29, 2020

Science Daily/La Jolla Institute for Immunology

A new study from researchers at La Jolla Institute for Immunology (LJI) and Erasmus University Medical Center (Erasmus MC) shows that even the sickest COVID-19 patients produce T cells that help fight the virus. The study offers further evidence that a COVID-19 vaccine will need to elicit T cells to work alongside antibodies.

The research, published June 26, 2020 in Science Immunology, also reveals that both Dutch and American patients have similar responses to the virus. "This is key to understanding how the immune response fights the virus," says LJI Professor Alessandro Sette, Dr. Biol. Sci., who co-led the study with Erasmus MC Virologist Rory de Vries, Ph.D. "You want vaccine approaches to be grounded in observations from rather diverse settings to ensure that the results are generally applicable."

For the study, the researchers followed ten COVID-19 patients with the most severe disease symptoms. All ten were admitted to the ICU at Erasmus University Medical Center, in the Netherlands, and put on ventilators as part of their care. Two of the patients eventually died of the disease. An in-depth look at their immune system responses showed that all ten patients produced T cells that targeted the SARS-CoV-2 virus. These T cells worked alongside antibodies to try to clear the virus and stop the infection.

"Activating these cells appears to be at least as important as the production of antibodies," says Erasmus MC Virologist Rory de Vries, Ph.D., who co-led the study with Sette.

These findings are in line with a recent Cell study from Sette, LJI Professor Shane Crotty, Ph.D., and LJI colleagues that showed a robust T cell response in individuals with moderate cases of COVID-19. In both studies, the T cells in these patients prominently targeted the "spike" protein on SARS-CoV-2. The virus uses the spike protein to enter host cells, and many vaccine efforts around the world are aimed at getting the immune system to recognize and attack this protein. The new study offers further evidence that the spike protein is a promising target and confirms that the immune system can also mount strong responses to other targets on the virus.

"This is good news for those making a vaccine using spike, and it also suggests new avenues to potentially increase vaccine potency," says Daniela Weiskopf, Ph.D., research assistant professor at LJI and first author of the new study.

The collaboration between scientists in La Jolla and the Netherlands is also a part of a larger picture, and emphasizes the highly collaborative philosophy adopted by the LJI group. Sette is a world leader in understanding what specific pieces (or epitopes) the immune system recognizes when it encounters a new microbe. The Sette lab's work in defining epitope sets to allow to measure SARS-CoV-2 T cell responses was a key element of the study.

In fact, LJI has become a hub for COVID-19 T cell studies, and Sette has sent out reagents to more than 60 labs around the world. "The study is also highly significant because it illustrates how science has no frontiers," says Sette. "To truly understand a global pandemic, our approach needs to be global, and we need to study effective immune response in people with different genetic backgrounds, living in different environments."

While the Cell paper followed San Diego residents, the new paper follows Dutch patients -- and the T cell responses were consistent in both populations. "This study is important because it shows this immune response in patients thousands of miles apart," says Weiskopf. "The same observation has now been strongly reproduced in different continents and different studies."

https://www.sciencedaily.com/releases/2020/06/200629124106.htm

Coronavirus: Social distancing accepted when people understand exponential growth

June 29, 2020

Science Daily/University of Cologne

Experiments among U.S. population show: When people fail to see the need for restrictions on public life, explaining the exponential increase of infections creates greater acceptance for measures taken to slow down the infection rate.

Researchers from the Social Cognition Center Cologne at the University of Cologne and from the University of Bremen report that participants in three experiments, each involving more than 500 adults in the United States, tended to assume the number of COVID-19 cases grew linearly with time, rather than exponentially. As a result, they underestimated actual virus growth. Interventions designed to help people avoid this bias led to an improved understanding of virus growth and increased support for social distancing measures compared with participants who did not receive such instructions.

The experiments were conducted by the social psychologist Dr Joris Lammers of the Social Cognition Center Cologne and the University of Bremen and his co-authors, the social psychologists Jan Crusius and Anne Gast, also from the University of Cologne. The article "Correcting misperceptions of exponential coronavirus growth increases support for social distancing" has been published in the current issue of Proceedings of the National Academy of Sciences.

The most effective way to stem the spread of a pandemic such as COVID-19 is what has come to be known as 'social distancing'. But the introduction of such measures is hampered by the fact that a sizeable part of the population fails to see their need. Many social scientists see the root of this perception in what they call the exponential growth bias. "In general, people have difficulty understanding exponential growth and erroneously interpret it in linear terms instead," explains first author Joris Lammers. The result is a gross underestimation of the growth of the infection rate and a misunderstanding of the potential to slow it down through social distancing. "Our current work tests the role of exponential growth bias in shaping the public's view on social distancing to contain the coronavirus's spreading."

Three studies were conducted during the mass spreading of the virus in the United States toward the end of March 2020. The first study focused on participants' understandings of linear growth, showing that many Americans mistakenly perceive the virus's exponential growth in linear terms. Interestingly, political orientation also played a role: conservatives were more prone to this misunderstanding than liberals. Studies 2 and 3 showed that instructing people to avoid the exponential growth bias significantly increases correct perceptions of the virus's growth and thereby support for social distancing. "Together, these results show the importance of statistical literacy to recruit support for fighting pandemics such as the coronavirus," said Lammers.

"Our results stand in contrast to earlier literature showing that the exponential growth bias is difficult to overcome," he explained. "The reason for this is that the current study focuses on a threat with great personal relevance and media presence, which likely increases subjective availability and thus the estimated probability of the risk."

Given that social distancing is the most effective way to combat the coronavirus currently available, these findings can have a significant impact: They show that bias, among other things, influences political opinions about matters of life and death, Lammers believes. Most important for team is to show the necessity of statistical literacy and to improve that skill among the general public.

https://www.sciencedaily.com/releases/2020/06/200629120142.htm

Collectivism drives efforts to reduce the spread of COVID-19

June 29, 2020

Science Daily/University of Kent

Research from the University of Kent has found that people who adopt a collectivist mindset are more likely to comply with social distancing and hygiene practices to help reduce the spread of COVID-19.

People who are more individualist are less likely to engage, partly due to beliefs in COVID-19 conspiracy theories, and feelings of powerlessness surrounding the pandemic.

This study suggests the need for the UK Government and other world leaders to consider promoting collectivism amongst the general public, and to combat the spread of conspiracy theories and other types of misinformation. Doing so may increase levels of engagement in practices to help reduce the spread of COVID-19.

The research was led by Mikey Biddlestone alongside Ricky Green and Professor Karen Douglas at the University of Kent's School of Psychology. A total of 724 participants completed an online questionnaire addressing their actions relating to social distancing and hygiene measures, their individualist-collectivist mindset, feelings of powerlessness surrounding the pandemic, and their beliefs in COVID-19 conspiracy theories such as the idea that COVID-19 was made in a Chinese laboratory.

Mikey Biddlestone said: "Interventions that focus on collective empowerment and champion a 'we are in this together' mentality could encourage people to comply with guidelines that will reduce the spread of COVID-19. Promoting collectivism could make a positive difference to future public health crises too, as leaders look to improve response strategies. A collectivist mindset might also make people less susceptible to conspiracy theories and misinformation that can negatively affect their behaviour."

 https://www.sciencedaily.com/releases/2020/06/200629120140.htm

How upregulation of a single gene by SARS-CoV-2 can result in a cytokine storm

June 29, 2020

Science Daily/IOS Press

The SARS-CoV-19 virus initially has a limited capability to invade, attacking only one intracellular genetic target, the aryl hydrocarbon receptors (AhRs). Yet it leads to widely diverse clinical symptoms, suggesting multiple pathogenic mechanisms. Writing in Restorative Neurology and Neuroscience, investigators describe how excessive activation of AhRs via the IDO1-kynurenine-AhR signaling pathway, which is used by many pathogens to establish infection, leads to "Systemic AhR Activation Syndrome" (SAAS). The authors also hypothesize that therapies targeting downregulation of AhRs and IDO1 genes should decrease severity of infection.

SAAS underlies inflammation, thromboembolism, and fibrosis that may lead to severe disease and death from COVID-19. When corona virus (CoV) infection persists, it activates IDO1 by massively releasing cytokines. This in turn perpetuates the already extensive viral activation of AhRs, and the self-limiting control mechanisms of the host immune response may derail, triggering the cytokine storm underlying the most severe symptoms of COVID-19.

"The SARS-CoV-19 virus is a living example of viral simplicity complicated by extreme target complexity," explains lead author Waldemar A. Turski, MD, PhD, Department of Experimental and Clinical Pharmacology, Medical University in Lublin, Poland. "Direct activation of AhRs by CoVs may lead to diverse sets of phenotypic disease pictures, depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs."

The authors demonstrate that CoVs are perfect viruses leaving nothing to chance and show how difficult it is to stop them after cell invasion. They describe how many of the features and symptoms of COVID-19 may be dependent on AhR activation, including thromboembolism, fibrosis, multiple organ injury, and brain damage. They also explore how environmental factors, such as urban dust and diesel fumes, may activate AhRs and make humans more prone to pathogens, including CoV. However, physical exercise plays a positive role in IDO1 function and downregulates AhRs.

The investigators hypothesize that when AhRs remain activated and clinical symptoms are mild, eliminating factors known to increase AhR activation or implementing factors known to suppress AhR activation should decrease the severity of infection. When the disease is fully established and symptoms are severe, IDO1 is believed to be continuously activated in addition to the CoV activation of AhRs. "Such a vicious cycle can only be efficiently interrupted by simultaneous downregulation of both AhR and IDO1. There is currently, however, no licensed medication specifically and simultaneously downregulating the activity of both AhR and IDO1," notes co-author Les Turski, MD, PhD, German Center for Neurodegenerative Diseases, Bonn, Germany.

Co-author Artur Wnorowski, PhD, Department of Biopharmacy, Faculty of Pharmacy, Medical University in Lublin, Poland, undertook an intriguing challenge that yielded surprising results. "I analyzed major databases to identify chemicals that downregulate both AhR and IDO1, or AhR gene expression. I selected 596 molecules and an in-depth analysis of 23,526 experiments involving these molecules identified either a single molecule that repeatedly reduced AhR and IDO1 or AhR gene expression in human cells."

The molecules were dexamethasone for AhR and IDO1, and calcitriol, the active form of vitamin D, which is also known to inhibit the spread of other viral infections, for the AhR gene. Likewise, tocopherol, a form of Vitamin E, might downregulate IDO1 and is known to play a positive role in response to viral infections and inflammation in aging. The authors call for epidemiological studies and prospective trials to determine if calcitriol and tocopherol supplementation should be recommended for the prevention of SARS-CoV-2 infections.

"Our concept is based on 40 years of research experience with the metabolism of tryptophan. Activation of IDO1 in immune cells leads to release of kynurenine, a tryptophan metabolite, activates AhR. IDO1 was the clue that brought us to the AhR-IDO1 axis concept and exposed the role that AhR may play in the pathogenesis of COVID-19," says Dr. Waldemar Turski.

The Editor-in-Chief of Restorative Neurology and Neuroscience, Professor Bernhard Sabel from the University of Magdeburg, Germany, in recognition of novelty of the authors' vision says: "The turning point defined by the authors' concepts requires critical review of our habits, our relationships with the environment, and our education and research in the context of AhR modulation. We seem to be at the very beginning of novel discovery pathways and only see the very tip of an iceberg of unknown size that may critically affect our future."

Because the authors are reporting on changes in gene expression only, their hypotheses need to be tested before claiming that there are benefits of any therapy in modulating the SARs-CoV-2 infection. Randomized controlled trials and large observational studies are needed.

https://www.sciencedaily.com/releases/2020/06/200629120126.htm