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

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

People with less body response to stress task had more PTSD signs after COVID-19 began

Study findings surprised researchers, who had expected the reverse, researcher says

August 31, 2020

Science Daily/Baylor University

People who did not have a large heart rate response to a stress task surprised researchers later -- after the onset of the COVID-19 pandemic -- when they showed more symptoms of post-traumatic stress disorder related to the crisis than others who also did the stress task and COVID-19 stress ratings.

Researchers had anticipated that the reverse would be true -- that those with higher heart rate reactions to the stress task would experience more distress related to COVID-19. Previous work shows individuals with a PTSD have higher responses to stress. But very few studies have examined heart rate responses to acute stress before the onset of a traumatic event, researchers said.

"The study shows that diminished biological arousal -- how the body responds when it is exposed to something startling or stressful -- before a global pandemic may predict PTSD symptoms related to the event," said principal investigator Annie T. Ginty, Ph.D., assistant professor of psychology and neuroscience at Baylor University.

The biological reactions were measured by blood pressure and heart rate, said co-author Danielle Young, Psy.D., research coordinator in the Baylor Behavioral Medicine Lab.

The study, published in the journal Psychosomatic Medicine, grew out of an ongoing study of undergraduate students at Baylor University.

"The research also showed that some college students were experiencing distress related to the pandemic in its earliest stages, even when social distancing was just beginning," Ginty said.

In the study's first phase, with 120 participants, researchers measured their resting heart rate and blood pressure before and during a standard acute psychological stress test. They asked students to do mental math, rather than writing down figures or using a calculator, and give the scorers verbal responses. In a four-minute test, they were asked to add consecutive single-digit numbers while remembering the most recent and adding it to the next number presented. They did this while being videotaped with a scorer present and looking at themselves in a mirror.

"The standard acute psychological stress task is meant to increase levels of stress by including requirements of cognitive effort, social evaluation, self-evaluation and competition," Ginty said. "The task substantially increases heart rate and feelings of stress."

The study's first phase, which ended in February 2020, was done in Central Texas. After the pandemic's onset, researchers launched a second phase between March 26 and April 5, sending participants a follow-up questionnaire about COVID-19. The participants were in 22 states after early campus closure due to COVID-19. When asked, none had tested positive for COVID-19 and 87.5 percent were living in a city/state with a "shelter in place" order.

The questionnaire included standard items used to measure PTSD symptoms of intrusion (dreaming about the event and having trouble staying asleep), hyperarousal (irritability and having trouble concentrating) and avoidance (trying not to think or talk about the event) in the seven days before they responded to the questionnaire.

The findings are in line with a previous study of soldiers, which showed that a lower response of cortisol -- the primary stress hormone -- to an acute psychological stress task before deployment predicted greater PTSD symptoms post deployment.

The present study supports growing evidence that lower biological arousal in response to psychological stress may be bad for health outcomes, particularly mental health outcomes. The findings support Ginty's previous work, which demonstrated that lower arousal to acute stress is associated with higher levels of perceived stress -- meaning that people rate their environment as more stressful.

Previous work also has shown that higher levels of biological arousal may be associated with developing PTSD symptoms. But those studies used what are considered passive tasks -- such as hearing loud bursts of noise. Lower biological responses to stress tasks that require participants to actively engage in the task may be a unique biomarker for mental health outcomes.

Ginty said that future research should aim for more comprehensive measures of biological reactivity and include a lifetime history of traumatic event exposure. However, the current study did account for childhood trauma and diagnosis of a mental health condition before the pandemic's onset.

"Since findings suggest that individuals with diminished arousal to active stress may be at greater risk for negative mental health outcomes, it could be helpful to offer preventive treatment or resources to them at the early stages of stress or trauma exposure," Ginty said.

https://www.sciencedaily.com/releases/2020/08/200831165700.htm

Loneliness predicts development of type 2 diabetes

September 15, 2020

Science Daily/King's College London

Published in the journal Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]), the study shows that it is the absence of quality connections with people and not the lack of contact that predicts the onset of type 2 diabetes, suggesting that helping people form and experience positive relationships could be a useful tool in prevention strategies for type 2 diabetes.

The results have implications in light of recent findings that people with diabetes are at greater risk of dying from COVID-19. The study indicates that prolonged loneliness may influence the development of diabetes, suggesting the experience of lockdown could potentially compound people's vulnerability in this pandemic if the loneliness continues for some time.

Loneliness occurs when an individual perceives that their social needs are not being met and reflects an imbalance between desired and actual social relationships. A fifth of adults in the UK and a third of adults in the USA report feeling lonely sometimes.

There is a growing interest in the role of loneliness in health and previous research has associated loneliness with increased risk of death and heart disease. This is the first study to investigate the experience of loneliness with later onset of type 2 diabetes.

The study analysed data from the English Longitudinal Study Ageing on 4112 adults aged 50 years and over which was collected at several times from 2002 to 2017. At the start of data collection all participants were free of diabetes and had normal levels of blood glucose.

The study showed that over a period of 12 years 264 people developed type 2 diabetes. and the level of loneliness measured at the start of data collection was a significant predictor of the onset of type 2 diabetes later on in life. This relationship remained intact when accounting for smoking, alcohol, weight, level of blood glucose, high blood pressure and cardiovascular disease. The association was also independent of depression, living alone and social isolation.

Lead author Dr Ruth Hackett from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King's College London said: 'The study shows a strong relationship between loneliness and the later onset of type 2 diabetes. What is particularly striking is that this relationship is robust even when factors that are important in diabetes development are taken into account such as smoking, alcohol intake and blood glucose as well as mental health factors such as depression. The study also demonstrates a clear distinction between loneliness and social isolation in that isolation or living alone does not predict type 2 diabetes whereas loneliness, which is defined by a person's quality of relationships, does.

She continued: 'I came up with the idea for the research during UK lockdown for the COVID-19 pandemic as I became increasingly aware and interested in how loneliness may affect our health, especially as it is likely that many more people were experiencing this difficult emotion during this period.'

According to the study a possible biological reason behind the association between loneliness and type 2 diabetes could be the impact of constant loneliness on the biological system responsible for stress, which, over time affects the body and increases the risk for diabetes.

'If the feeling of loneliness becomes chronic,' explained Dr Hackett. 'Then everyday you're stimulating the stress system and over time that leads to wear and tear on your body and those negative changes in stress-related biology may be linked to type 2 diabetes development.'

Another explanation for the findings could be biases in our thinking that may perpetuate the association between loneliness and diabetes as when people feel lonely, they expect people will react to them negatively which makes it more difficult to form good relationships.

https://www.sciencedaily.com/releases/2020/09/200915105943.htm

Older adults with existing depression show resilience during the pandemic

August 19, 2020

Science Daily/University of California - Los Angeles Health Sciences

A study involving older adults with pre-existing major depressive disorder living in Los Angeles, New York, Pittsburgh, and St Louis found no increase in depression and anxiety during the COVID-19 pandemic.

Researchers from five institutions, including UCLA, found that the older adults, who were already enrolled in ongoing studies of treatment resistant depression, also exhibited resilience to the stress of physical distancing and isolation. The findings were published in peer-reviewed journal, The American Journal of Geriatric Psychiatry.

"We thought they would be more vulnerable to the stress of COVID because they are, by CDC definition, the most vulnerable population," said Helen Lavretsky, MD, a professor-in-residence of psychiatry and biobehavioral sciences at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA. "But what we learned is that older adults with depression can be resilient. They told use that coping with chronic depression taught them to be resilient"

For the study, researchers conducted interviews with the participants, all of whom were over the age of 60, with an average age of 69, during the first two months of the pandemic. Using two screening assessments of depression and anxiety, PHQ-9 and PROMIS, researchers found no changes in the participants' depression, anxiety or suicidality scores before and during the pandemic.

Researchers further determined that:

• Participants were more concerned about the risk of contracting the virus than the risks of isolation.

• While all maintained physical distance, most did not feel socially isolated and were using virtual technology to connect with friends and family.

• While they were coping, many participants said their quality of life was lower, and they worry their mental health will suffer with continued physical distancing.

• Participants were upset by the inadequate governmental response to the pandemic.

Based on the findings, the study authors wrote that policies and interventions to provide access to medical services and opportunities for social interaction are needed to help older adults maintain mental health and quality of life as the pandemic continues.

Lavretsky said many participants reported their quality of life to be lower, and they worried that their mental health will suffer with continued physical distancing. She said further research is needed to determine the impact of the pandemic over time.

She added that the findings offer takeaways for others while weathering the pandemic. "These older persons living with depression have been under stress for a longer time than many of the rest of us. We could draw upon their resilience and learn from it."

The study identified several self-care and coping strategies used by the participants, which included maintaining regular schedules; distracting themselves from negative emotions with hobbies, chores, work or exercise; and using mindfulness to focus on immediate surroundings and needs without thinking beyond the present.

The authors further emphasized that access to mental health care and support groups, and continued social interaction are needed to help older adults whether the pandemic.

https://www.sciencedaily.com/releases/2020/08/200819170223.htm

COVID-19 increased anxiety, depression for already stressed college students

Study shows unprecedented increase in mental health challenges among undergraduates

July 27, 2020

Science Daily/Dartmouth College

College students were more anxious and depressed during the initial outbreak of COVID-19 than they were during similar time frames in previous academic years, according to a Dartmouth study.

The research also found that sedentary behavior increased dramatically during the onset of the public health crisis in early March.

The study, published in the Journal of Medical Internet Research, used a mix of smartphone sensing and digital questionnaires from more than 200 students participating in a research program that is tracking mental health throughout their undergraduate years.

"COVID-19 had an immediate negative impact on the emotional well-being of the college students we studied," said Jeremy Huckins, a lecturer on psychological and brain sciences at Dartmouth. "We observed a large-scale shift in mental health and behavior compared to the observed baseline established for this group over previous years."

Self-reported symptoms of depression and anxiety within the student research group spiked noticeably at the onset of COVID-19. At the time, major policy changes related to COVID-19 were also being put in place, including the request that students leave campus and the switch to remote learning.

These changes coincided with the end of classes and final exams, already one of the most stressful times for students in any academic term.

According to the study, anxiety and depression decreased slightly after the final exam period as students settled into shelter-in-place locations. This suggested some resilience in the face of COVID-19, but levels remained consistently higher than similar periods during previous academic terms.

Unlike previous terms studied, sedentary time increased dramatically during this year's spring break period.

"This was an atypical time for these college students. While spring break is usually a period of decreased stress and increased physical activity, spring break 2020 was stressful and confining for the students participating in this study. We suspect that this was the case for a large number of college students across the country," said Huckins.

The study used StudentLife, a sensing app developed at Dartmouth, to collect information from student volunteers. StudentLife passively collects behavioral information from user's smartphones such as duration of phone usage, number of phone unlocks, sleep duration, and sedentary time.

Data on depression and anxiety were collected using weekly, self-reported assessments also administered through the StudentLife app.

"This is the first time we have used sensor data from phones to give us unique behavioral insights into the reaction of students to the onset of the pandemic on a college campus," said Andrew Campbell, the Albert Bradley 1915 Third Century Professor of computer science at Dartmouth and one of the lead researchers of the StudentLife study. "We plan to further analyze how these students adjusted both physically and mentally during remote learning that leads on from this study."

In the research, the team also reported a connection between anxiety and COVID-19 news coverage. The link between depression and news reporting was apparent, but not as strong. As news coverage intensified, there was an increase in sedentary behavior and a longer duration of phone usage.

According to the study, the decrease in the number of locations visited was consistent with the social distancing and shelter-in-place policies implemented by local governments.

The study's findings on the uptake of social distancing recommendations contrasts with other research of college students in which governmental social distancing policies were not followed. Findings in the current study are also contrary to media depictions of college-age students flouting social distancing recommendations during the spring break period.

"Many people wouldn't expect college students to listen to social distancing orders, but these students did. We found that when social distancing was recommended by local governments, students were more sedentary and visited fewer locations on any given day," said Huckins. "Clearly the impact of COVID-19 extends beyond the virus and its direct impacts. An unresolved question is if mental health and physical activity will continue to degrade over time, or if we will see a recovery, and how long that recovery will take."

The research is part of a multiyear study focusing on the mental health of undergraduate students as they progress through their undergraduate careers. The complete study combines smartphone mobile sensing with functional neuroimaging.

"When we set out two years ago to follow 200 students across their college experiences, we could never have anticipated the inflection point in our data as a result of such a catastrophic event as the pandemic," added Campbell.

Upon completion of the full study, researchers will be able to extend their findings on the disruption at the start of the COVID-19 pandemic to the long-term impact of remote learning and social isolation that the students are experiencing.

More information on the StudentLife research program can be found at: https://studentlife.cs.dartmouth.edu

https://www.sciencedaily.com/releases/2020/07/200727114731.htm

Type 1 interferon deficiency: Biomarker of patients at risk of severe COVID-19

July 17, 2020

Science Daily/INSERM (Institut national de la santé et de la recherche médicale)

Which patients will develop a severe form of Covid-19? This is a key question that needs to be answered to improve the individual management and prognosis of patients. In a study published in Science on July 13, teams from AP-HP, Inserm, Université of Paris, Institut Pasteur and Institut Imagine describe a unique and unexpected immunological phenotype in severe and critical patients, consisting of a severely impaired response of interferon (IFN) type I, associated with a persistent blood viral load and an excessive inflammatory response. These data suggest that IFN type I deficiency in the blood could be a hallmark of severe forms of Covid-19. It also supports the potential value of therapeutic approaches that combine early administration of IFN, with appropriate anti-inflammatory therapy targeting IL-6 or TNF-α, in patients preventing severe disease forms.

Approximately 5% of people with Covid-19 progress to a severe or critical form, including the development of severe pneumonia that progresses to acute respiratory distress syndrome. While these forms sometimes occur early in the course of the disease, clinical observations generally describe a two-stage progression of the disease, beginning with a mild to moderate form, followed by respiratory aggravation 9 to 12 days after the onset of the first symptoms. This sudden progression suggests deregulation of the host inflammatory response.

A growing number of indications suggest that this aggravation is caused by a large increase in cytokines. This runaway inflammatory response is correlated with massive infiltration in the lungs of innate immune cells, namely neutrophils and monocytes, creating lung damage and acute respiratory distress syndrome.

By analogy with a genetic disease leading to a similar pulmonary pathology identified at Institut Imagine by the team of Inserm researcher Frédéric Rieux-Laucat, the initial hypothesis assumed excessive production of interferon (IFN) type I, a marker of the response to infections. However, in seriously ill patients, the teams of Darragh Duffy (Dendritic Cell Immunobiology Unit, Institut Pasteur/Inserm), Frédéric Rieux-Laucat (Laboratory of Immunogenetics of Pediatric Autoimmune Diseases at Institut Imagine -- Inserm/Université de Paris), Solen Kernéis (Mobile Infectiology Team, AP-HP. Centre -- Université of Paris) and Benjamin Terrier (Department of Internal Medicine, AP-HP. Centre -- Université of Paris) show that the production and activity of type-I IFN are strongly reduced in the most severe forms of Covid-19.

In addition, there is a persistent blood viral load, indicating poor control of viral replication by the patient's immune system which leads to an ineffective and pathological inflammatory response. The inflammation, caused by the transcription factor NF-kB, also leads to increased production and signaling of tumor necrosis factor (TNF)-alpha and the pro-inflammatory cytokine interleukin IL-6.

Distinct type-I IFN responses may be characteristic of each stage of the disease

This low signature of type-I IFN differs from the response induced by other respiratory viruses such as human respiratory syncitial virus or influenza A virus, both of which are characterized by high production of type-I IFN.

The study also showed that low levels of type-I IFN in plasma precede clinical worsening and transfer to intensive care. Levels of circulating Type 1 IFN could even characterize each stage of disease, with the lowest levels observed in the most severe patients. These results suggest that in SARS-CoV-2 infection, the production of type-I IFN is inhibited in the infected host, which could explain the more frequent severe forms in individuals with low production of this cytokine, such as the elderly or those with co-morbidities.

Therefore, type-I IFN deficiency could be a signature of severe forms of COVID-19 and could identify a high-risk population.

These results further suggest that the administration of IFN-alpha/Beta combined with anti-inflammatory therapy targeting IL-6 or TNF-α, or corticosteroids such as dexamethasone, in the most severe patients could be a therapeutic avenue to be evaluated for severe forms of COVID-19.

https://www.sciencedaily.com/releases/2020/07/200717101015.htm

Chest x-rays show more severe COVID-19 in non-white patients

July 16, 2020

Science Daily/Radiological Society of North America

Racial/ethnic minority patients admitted to the hospital with COVID-19 infection are more likely to have more severe disease on chest X-rays than white/non-Hispanic patients, increasing the likelihood of adverse outcomes, such as intubation or death, according to a study published in the journal Radiology.

Emerging data show that racial/ethnic minorities have been disproportionately affected by COVID-19. Socioeconomic factors and pre-existing medical conditions like hypertension are likely contributing factors to this disparity. Furthermore, limited English proficiency may introduce additional linguistic and health literacy barriers to care, potentially resulting in delays seeking medical attention and greater severity of disease at the time of admission to the hospital with COVID-19 infection.

Radiologists from Massachusetts General Hospital (MGH) saw these disparities firsthand in April among patients admitted to the hospital with confirmed COVID-19 infection, and at one of the hospital's respiratory infection clinics in Chelsea, a city just north of Boston that is home to a predominantly Spanish-speaking Hispanic community. A significant proportion of the patients who visited the Chelsea clinic had COVID-19, and the level of disease the radiologists observed on chest imaging was markedly more severe than that seen at other respiratory infection clinics in Boston. These disparities were more evident among patients admitted to the hospital with confirmed COVID-19 infection.

"It got to the point where half of our patient population admitted with COVID-19 were underrepresented minorities," said study coauthor Efren J. Flores, M.D., a radiologist at MGH.

Dr. Flores and colleagues set out to study these observed disparities in greater detail with an eye toward developing a better understanding of some of the factors involved. They hope to use this information to guide risk mitigation strategies and improve outcomes among racial/ethnic minority groups. They looked at data from 326 patients hospitalized with confirmed COVID-19 infection between March 27 and April 10, 2020. Analysis of chest X-ray results revealed that non-white patients had significantly more severe lung disease on admission than white/non-Hispanic patients. Increased disease severity on chest X-rays increased the likelihood of adverse clinical outcomes, including admission to the intensive care unit, intubation and death.

As expected, the increased severity of lung disease on chest X-rays among non-white patients correlated with a combination of factors, including delay in seeking care at the hospital, higher prevalence of pre-existing comorbidities and limited English proficiency.

"Limited English proficiency is an additional socioeconomic factor that really influences many aspects of access to care," Dr. Flores said. "When we were first learning how the disease spreads, there was all this rapidly evolving information coming out that was not available in languages other than English, and that lag in availability of actionable health information for non-English speaking individuals was really critical for many patients trying to navigate a complex medical system with a disease from a virus that is so aggressive."

The connection between limited English proficiency and disease severity underscores the importance of having multilingual, culturally tailored health information available, Dr. Flores said, especially as the number of infections climbs in different parts of the country.

Disparities in access to care and disease severity are not limited to linguistic barriers. Racial/ethnic non-white communities disproportionately experience lower socioeconomic status, adding another layer of complexity when accessing care. Living and working arrangements also likely played a role in the severity of COVID-19 among these patients, the study authors said. Racial and ethnic minority populations tend to live in multigenerational households and communities of higher population density, making social distancing difficult. In addition, they are more often employed in jobs not conducive to remote work with limited paid time off, thus increasing their exposure to COVID-19.

"Many of these patients delay their care because they're considered essential workers and they don't have a lot of sick leave, but also it's difficult for them to leave because they are living on a weekly paycheck and have other dependents," Dr. Flores said. "It wasn't uncommon for us to go into the medical record when we were interpreting their exams and see that many of them worked at grocery stores or warehouses."

The study findings highlight the important role radiologists play in providing earlier identification of higher-risk patients and developing multidisciplinary collaborations to help address these disparities, according to Dr. Flores.

"Health equity is every medical specialty's responsibility, but I believe radiology is uniquely positioned to take a bigger role not only in population health but in public health efforts," he said. "Our ability to provide care in different settings is what allowed us to make the clinical observation that patients coming to this one particular clinic and those being admitted to the hospital were presenting with a higher rate of positive findings that were also more severe. That really offered a window into the disparities that were translating into greater disease severity and worse outcomes."

Moving forward, the findings of this study could assist radiologists in the development of algorithms to identify vulnerable and at-risk populations. This could spur collaborations with other medical specialties, community stakeholders, and public health initiatives to enhance the effectiveness of public health interventions that increase access to care.

"We did this study not only to gain a better understanding of these emerging disparities, but also to discover how we can use this information to craft a better path towards equity together," Dr. Flores said.

https://www.sciencedaily.com/releases/2020/07/200716144710.htm

Dangerous blood clots form in leg arteries of COVID-19 patients

July 16, 2020

Science Daily/Radiological Society of North America

COVID-19 is associated with life-threatening blood clots in the arteries of the legs, according to a study published in Radiology. Researchers said COVID-19 patients with symptoms of inadequate blood supply to the lower extremities tend to have larger clots and a significantly higher rate of amputation and death than uninfected people with the same condition.

COVID-19's association with blood clots in the pulmonary arteries is well-established. Less is known about the virus' connection to lower extremity arterial thrombosis, a condition characterized by blood clots in the arteries that impede the flow of oxygenated blood to the lower extremities.

During the peak of the COVID-19 pandemic in New York City, radiologists at the city's Montefiore Medical Center observed an increase in patients testing positive for lower extremity arterial thrombosis on CT angiography exams. The patients had arrived at hospitals with coldness, pain or discoloration of their legs. Frequently these symptoms of leg ischemia, a condition in which blood flow to the lower extremities is restricted, were accompanied by respiratory distress, cough, fever and altered mental status.

The alarming trend prompted the researchers to look more closely at a possible connection between COVID-19 and lower extremity arterial thrombosis and whether people with the virus had a worse prognosis.

In March and April 2020, they identified 16 COVID-19-positive patients, average age 70, who underwent CT angiography of the lower extremities for symptoms of leg ischemia. These patients were compared with 32 COVID-19-negative patients, average age 71, who underwent CT angiography with similar symptoms in previous years and who were well matched with COVID-19 cohort for demographic and clinical characteristics.

All patients with COVID-19 infection undergoing lower extremity CT angiography had at least one clot in the leg, compared with only 69% of controls. The clots in the COVID-19 patients were significantly larger and affected arteries higher up in the leg with greater frequency than those in controls. Death or limb amputation was more common in the COVID-19 patients.

"We found that arterial thrombosis associated with COVID-19 infection was characterized by dire outcomes, namely strikingly increased rates of amputation and death, which in our series were 25% and 38%, respectively," said study lead author Inessa A. Goldman, M.D., a radiologist at Montefiore and assistant professor at Albert Einstein College of Medicine in New York City. "For comparison, the rate of both amputation and death was only 3% among controls. It is unclear whether the patients' concurrent COVID-19-related pneumonia, the virulence of the COVID-19-related clotting disorder or delayed initial arrival to the hospital contributed to these outcomes."

COVID-19 patients presenting with symptoms of leg ischemia only were more likely to avoid amputation or death than patients who had symptoms of ischemia and systemic symptoms including cough, respiratory distress or failure, hypoxia, fever, or altered mental status.

"In our cohort none of the five patients presenting with complaints pertaining to leg symptoms only, such as pain or discoloration, without systemic symptoms sustained amputation or died," Dr. Goldman said.

Dr. Goldman noted that with infection rates rising in many parts of the country, it is important that physicians be mindful of the connection between COVID-19 and lower extremity arterial thrombosis.

"Awareness of lower extremity arterial thrombosis as a possible complication of COVID-19 infection is important for all providers who take care of these patients, because early diagnosis is usually crucial for limb preservation in lower extremity ischemia," she said.

COVID-19's association with lower extremity arterial thrombosis is likely related to a combination of factors, Dr. Goldman said, including an increased tendency of the blood to clot, damage to the lining of the arteries, and immune reactions tied to the SARS-CoV-2 virus and COVID-19 infection.

"This continues to be an area of intense study around the world," she said.

https://www.sciencedaily.com/releases/2020/07/200716144706.htm

Vaccine additives can enhance immune flexibility -- Implications for flu and SARS-CoV-2

July 16, 2020

Science Daily/Emory Health Sciences

A vaccine additive known as an adjuvant can enhance responses to a vaccine containing the exotic avian flu virus H5N1, so that both rookie and veteran elements of the immune response are strengthened, according to results from an Emory Vaccine Center study.

The findings have implications for the effort to develop vaccines against multiple strains of flu, as well as the current push for vaccines against SARS-CoV-2. The Emory study was a test of what happens when the body sees something new -- in contrast to seasonal flu vaccination, which often re-activates the same memory B cells the immune system relied upon in past years.

The study provides guidance on how adjuvants might become part of a proposed "universal" flu vaccine, aimed at protecting people against a wider variety of influenza strains. In addition, vaccine designers are considering how to optimize immune responses against SARS-Cov-2, which few had encountered before 2020.

The results were published online July 13 by Proceedings of the National Academy of Sciences.

"We saw that an adjuvant makes it possible to efficiently engage both memory and naive B cells, expanding the repertoire of the antibody immune response to influenza," says first author Ali Ellebedy, PhD, who did the study while he was a postdoctoral fellow in Rafi Ahmed's lab at Emory Vaccine Center.

"For a new pathogen like SARS-CoV-2, nobody has immunity," Ahmed says. "So the important thing is to have the vaccine bring out good responses from naïve B cells, whose frequency is low."

"For universal flu, the situation is more complicated. You want to bring out both the cross-reactive memory cells and the naïve strain-specific cells," adds Ahmed, whose lab is part of a NIH-funded consortium developing flu vaccine candidates. "Looking ahead, adjuvants are going to be an important element of universal flu vaccine research."

The particular adjuvant studied in the paper is called AS03, whose manufacturer GlaxoSmithKline is making it available for COVID-19 vaccine trials. The AS03 adjuvant could be relevant for extending the efficacy of limited doses of protein or viral subunit-based vaccines, but less so for newer mRNA-based vaccines, Ahmed says.

The Hope Clinic study recruited 50 healthy young adults, who were (most likely) exposed to other flu viruses and vaccines earlier in their lives. The H5N1 vaccine, with AS03, was approved by the FDA in 2013 and is part of the national stockpile in case of pandemic flu. More information about the AS03-adjuvanted flu vaccine is available from the FDA.

Emory researchers had previously observed that when the immune system encounters an unfamiliar flu virus, which occurred for many during the 2009 H1N1 pandemic, the antibodies produced are able to neutralize a broader range of viruses. This came from the skew of the antibodies toward the "stem" (or stalk) region of the viral hemagglutinin protein, versus the "head." The stem region doesn't mutate and change as much as the head from year to year.

A similar phenomenon occurred in the H5N1 study, because the head region of the virus was unfamiliar, but the stem region was not. Without an adjuvant, the immune response to a low dose of the H5N1 flu vaccine was poor, the researchers found.

But with the adjuvant, immune responses changed markedly between the first and second dose. A week after the first adjuvanted vaccine dose, broadly cross-reactive antibodies produced by the immune system were mostly directed against the stem. This first wave came mostly from pre-existing memory B cells. After the second dose, the antibodies were more directed against the head, coming from strain-specific naïve B cells.

The researchers also offered an explanation for the shift in the antibody response after the second dose: essentially, the immune system is getting in its own way. After the second vaccination, the antibodies against the stem region are still in the body and they appear to be covering up those parts of the viral hemagglutinin protein, a phenomenon called "epitope blocking."

"This is something that many flu vaccine studies have observed, but now we have a possible mechanistic explanation and good evidence for it," Ahmed says.

https://www.sciencedaily.com/releases/2020/07/200716122917.htm

Scientists uncover SARS-CoV-2-specific T cell immunity in recovered COVID-19 and SARS patients

July 16, 2020

Science Daily/Duke-NUS Medical School

The T cells, along with antibodies, are an integral part of the human immune response against viral infections due to their ability to directly target and kill infected cells. A Singapore study has uncovered the presence of virus-specific T cell immunity in people who recovered from COVID-19 and SARS, as well as some healthy study subjects who had never been infected by either virus.

The study by scientists from Duke-NUS Medical School, in close collaboration with the National University of Singapore (NUS) Yong Loo Lin School of Medicine, Singapore General Hospital (SGH) and National Centre for Infectious Diseases (NCID) was published in Nature. The findings suggest infection and exposure to coronaviruses induces long-lasting memory T cells, which could help in the management of the current pandemic and in vaccine development against COVID-19.

The team tested subjects who recovered from COVID-19 and found the presence of SARS-CoV-2-specific T cells in all of them, which suggests that T cells play an important role in this infection. Importantly, the team showed that patients who recovered from SARS 17 years ago after the 2003 outbreak, still possess virus-specific memory T cells and displayed cross-immunity to SARS-CoV-2.

"Our team also tested uninfected healthy individuals and found SARS-CoV-2-specific T cells in more than 50 percent of them. This could be due to cross-reactive immunity obtained from exposure to other coronaviruses, such as those causing the common cold, or presently unknown animal coronaviruses. It is important to understand if this could explain why some individuals are able to better control the infection," said Professor Antonio Bertoletti, from Duke-NUS' Emerging Infectious Diseases (EID) programme, who is the corresponding author of this study.

Associate Professor Tan Yee Joo from the Department of Microbiology and Immunology at NUS Yong Loo Lin School of Medicine and Joint Senior Principal Investigator, Institute of Molecular and Cell Biology, A*STAR added, "We have also initiated follow-up studies on the COVID-19 recovered patients, to determine if their immunity as shown in their T cells persists over an extended period of time. This is very important for vaccine development and to answer the question about reinfection."

"While there have been many studies about SARS-CoV-2, there is still a lot we don't understand about the virus yet. What we do know is that T cells play an important role in the immune response against viral infections and should be assessed for their role in combating SARS-CoV-2, which has affected many people worldwide. Hopefully, our discovery will bring us a step closer to creating an effective vaccine," said Associate Professor Jenny Low, Senior Consultant, Department of Infectious Diseases, SGH, and Duke-NUS' EID programme.

"NCID was heartened by the tremendous support we received from many previous SARS patients for this study. Their contributions, 17 years after they were originally infected, helped us understand mechanisms for lasting immunity to SARS-like viruses, and their implications for developing better vaccines against COVID-19 and related viruses," said Dr Mark Chen I-Cheng, Head of the NCID Research Office.

The team will be conducting a larger study of exposed, uninfected subjects to examine whether T cells can protect against COVID-19 infection or alter the course of infection. They will also be exploring the potential therapeutic use of SARS-CoV-2-specific T cells.

https://www.sciencedaily.com/releases/2020/07/200716101536.htm

Earlier lockdown restrictions linked to greater reduction in new COVID-19 cases

Findings should help inform policies as countries prepare to impose or lift restrictions

July 15, 2020

Science Daily/BMJ

Physical distancing measures, such as closing schools, workplaces, and public transport, and restricting mass gatherings, are associated with a meaningful reduction in new covid-19 cases, finds a study published by The BMJ today.

The data, gathered from 149 countries and regions, also show that implementing lockdown restrictions earlier was associated with a greater reduction in new cases.

"These findings might support policy decisions as countries prepare to impose or lift physical distancing measures in current or future epidemic waves," say the researchers.

Without evidence for effective treatments or a successful vaccine for covid-19, physical distancing has been recommended to minimise transmission, and thus reduce risk for the most vulnerable in society.

Physical distancing also therefore reduces pressure on public health and healthcare services, and allows time for the prevention and management of the disease. But 'real-life' data on the effectiveness of physical distancing measures are scarce.

To address this evidence gap, a team of UK and US researchers set out to compare the change in new cases (incidence) of covid-19 before and up to 30 days after implementation of physical distancing measures in the early stages of the pandemic.

Their findings are based on daily reported cases of covid-19 for 149 countries or regions that implemented one or more of five physical distancing measures -- closures of schools, workplaces, and public transport, restrictions on mass gatherings and public events, and restrictions on people's movement within countries or regions ('lockdown') -- between 1 January and 30 May 2020.

On average, physical distancing measures were first implemented 9 days after the first reported case. However, some countries took longer to implement measures, including Thailand (58 days), Australia (51 days), Canada (46 days), Sri Lanka and the UK (45 days), Finland and Malaysia (42 days), and Cambodia, Sweden, and the US (40 days).

On average, implementation of any physical distancing measure was associated with an overall reduction in covid-19 incidence of 13% over the study period.

In combination with school and workplace closure, restriction on mass gatherings seemed to be a key component associated with a decrease in covid-19 incidence.

However, closure of public transport was not associated with any additional reduction in covid-19 incidence when the other four physical distancing measures were in place -- likely as a result of fewer people using public transport.

The data also show that earlier implementation of lockdown together with other physical distancing measures was associated with a larger reduction in the incidence of covid-19.

This is an evaluation of natural experiments using observational methods, so is limited in its ability to establish cause. The researchers also point to some other limitations, such as being unable to assess compliance with physical distancing or take account of other measures (like use of face coverings by the public and mobile phone apps for contact tracing and isolation) that might have helped reduce transmission, due to lack of suitable data.

However, this is a large study with a robust analytical approach, and the results were similar after testing a range of alternative approaches to analyses, suggesting that the primary findings are robust to alternative analytic scenarios.

Further research is needed to provide more definitive answers about the extent, intensity, combinations, and timing of physical distancing measures, they write.

The researchers suggest that as the pandemic continues to evolve, "it will be crucial to repeat and extend this analysis to assess the impacts of interventions in the longer term, as well as to study combinations and sequencing of the lifting of physical distancing restrictions."

This study provides important preliminary evidence for the effectiveness of physical distancing measures in controlling the covid-19 pandemic, says Thomas May at Washington State University, in a linked editorial.

But he warns that failures in testing practices and data collection in many countries means that caution is needed when interpreting the findings.

"We must be careful not to mislead or overplay politically convenient findings and risk violating the public trust necessary for an effective pandemic response," he writes.

He points out that calls for a coordinated, global public health infrastructure for a pandemic response have been growing for decades, and says "only by acknowledging our failures in systematic testing and data collection can we learn from our mistakes and avoid repeating them."

https://www.sciencedaily.com/releases/2020/07/200715190744.htm

Social distancing and COVID-19: A law of diminishing returns

Research finds distancing helps ease the burden on hospitals -- but only to a point

July 15, 2020

Science Daily/Washington University in St. Louis

The first case of the novel coronavirus, COVID-19, in the United States was in late January. By mid-March, "social distancing" had entered the public lexicon. People altered their routines and local jurisdictions suggested, urged, or required changes meant to slow the disease's spread.

By the end of June, however, public health officials and news outlets were talking about a second wave. In July, many states were pausing or reversing their plans to reopen while, for the second time, hospital systems worried about running out of room.

What could we have done better?

In an "editor's pick" paper published today in the journal Chaos of the American Institute of Physics, Washington University in St. Louis researchers in the lab of Rajan Chakrabarty, associate professor in the department of Energy, Environmental and Chemical Engineering at the McKelvey School of Engineering, modeled the interplay between the duration and intensity of social distancing. They found a law of diminishing returns, showing that longer periods of social distancing are not always more successful when it comes to slowing the spread, and that any strategy that involves social distancing requires other steps be taken in tandem.

"Conventional wisdom was, the more intense and long-term the social distancing, the more you will curb the disease spread," Chakrabarty said

"But that is true if you have social distancing implemented with contact tracing, isolation and testing. Without those, you will give rise to a second wave."

Added Payton Beeler, a second year doctoral student in Chakrabarty's lab, who also worked with Pai Liu, a postdoctoral fellow: "What we have found is that if social distancing is the only measure taken, it must be implemented extremely carefully in order for its benefits to be fully realized."

Their susceptible, exposed, infected, and recovered (SEIR) dynamics model used data gathered by Johns Hopkins University between March 18 and March 29, a period marked by a rapid surge in COVID-19 cases and the onset of social distancing in most US states. Calibrating their model using these datasets allowed the authors to analyze unbiased results that had not yet been affected by large-scale distancing in place.

Unique to this project was the use of age stratification; the model included details on how much people of different age groups interact, and how that affects the spread of transmission.

No matter what strategy they looked at, one thing was clear, Chakrabarty said: "Had social distancing been implemented earlier, we probably would've done a better job."

Researchers found that, over the short-term, more distancing and less hospital demand go hand in hand -- but only up to two weeks. After that, time spent distancing does not benefit hospital demand as much; society would have to increase social distancing time exponentially in order to see a linear decrease in hospital demand.

Thus the diminishing return: Society would see smaller and smaller benefits to hospital demand the longer it spent social distancing.

If social distancing "alone" is to be implemented longer than two weeks, a moderate shut down, say between 50-70%, could be more effective for the society than a stricter complete shut-down in yielding the largest reduction in medical demands.

Another strategy for flattening the curve involves acting intermittently, alternating between strict social distancing and no distancing to alleviate the strain on hospitals -- as well as some of the other strains on the economy and well-being imposed by longer-term distancing.

According to the model, the most efficient distancing- to- no-distancing ratio is 5 to 1; one day of no distancing for every five days at home. Had society acted in this way, hospital burden could have been reduced by 80%, Chakrabarty said. Exceeding this ratio, the model showed a diminishing return.

Critically, the researchers note that social distancing policy as a whole-of-government approach could not be successful without the implementation of wide-spread testing, contact tracing, and isolation of those found to be infected.

"And you have to do it aggressively," Chakrabarty said. "If you do not, what you're going to do, the moment you lift social distancing, is give rise to a second wave."

That's because the people who are leaving their homes after distancing themselves are, ostensibly, all susceptible to COVID-19.

"Bending the curve using social distancing alone is analogous to slowing down the front of a raging wildfire without extinguishing the glowing embers," said Chakrabarty, whose other line of research focuses on the impacts of wildfires on climate and health.

"They are waiting to start their own fires once the wind carries them away."

The model cannot inform strategies going forward because it used data collected in March, before any large-scale social distancing was implemented. But Chakrabarty said it may be able to inform our actions if we find ourselves in a similar situation in the future.

"Next time, we must act faster, and be more aggressive when it comes to contact tracing and testing and isolation," Chakrabarty said. "Or else this work was for nothing."

https://www.sciencedaily.com/releases/2020/07/200715160005.htm