Study links abnormally high blood sugar with higher risk of death in COVID-19 patients not previously diagnosed with diabetes

July 10, 2020

Science Daily/Diabetologia

New research from Wuhan, China shows that, in patients with COVID-19 but without a previous diagnosis of diabetes, abnormally high blood sugar is associated with more than double the risk of death and also an increased risk of severe complications. The study is by Dr Yang Jin, Union Hospital and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, and colleagues. The study is published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]).

Previous studies have established that hyperglycaemia (abnormally high blood sugar) is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, heart attacks, trauma and surgery, among other conditions. A number of studies have also shown links between diabetes and poor outcomes in COVID-19 patients. However, direct correlation between fasting blood glucose (FBG) level at admission to hospital and clinical outcomes of COVID-19 patients without diagnosed diabetes has not been well established. In this new study the authors examined the association between FBG on admission and the 28-day mortality of COVID-19 patients without previously diagnosed diabetes in two hospitals.

The retrospective study assessed all consecutive COVID-19 patients with a known outcome at 28-days and FBG measurement at admission from 24 January 2020 to 10 February 2020 in two hospitals based in Wuhan, China. Demographic and clinical data, 28-day outcomes, in-hospital complications and CRB-65 scores of COVID-19 patients in the two hospitals were analysed. The CRB-65 score is an effective measure for assessing the severity of pneumonia and is based on four indicators: level of confusion, respiratory rate (over 30 breaths per min), systolic blood pressure (90 mmHg or less) or diastolic blood pressure (60 mmHg or less), and age (65 years or over).

A total of 605 COVID-19 patients were enrolled, including 114 who died in hospital. The median age of participants was 59 years and 322 (53.2%) were men. A total of 208 (34%) had one or more underlying conditions (but not diagnosed diabetes), of which high blood pressure was the most common. Almost one third (29%) of patients fell into the highest category of FBG on admission (7.0 mmol/L) which if found consistently would result in a diagnosis of type 2 diabetes. A further 17% were in the range that would be considered pre-diabetic (6.1-6.9 mmol/L), while more than half (54%) were in the 'normal' FBG range of 6.0 mmol/L or below.

The results showed that patients in the highest FBG group were 2.3 times more likely to die than those in the lowest, a statistically significant result. Those in the middle (pre-diabetic) FBG group were 71% more likely to die than those in the lowest group, although this result only had borderline statistical significance. The data also showed that men were 75% more likely to die than women; and that patients with higher CRB65 scores (and thus worse pneumonia) were also at higher risk of death: those with a score of 3-4 were more than 5 times more likely to die than those with a score of 0, while for those with a score of 1-2 there was a 2.7 times increased risk.

When looking at FBG and CRB65 scores together, the patients in the highest FBG group had an increased risk of death compared to the lowest, regardless of whether or not the CRB65 score was zero or higher, further underlining that FBG independently increases the risk of death in COVID-19 patients. However, the increased risk of death for the highest FBG group was lower in patients with CRB65 scores of above zero compared with those with a CRB65 score of zero. The risk of complications was also found to be 4 times higher in the highest FBG group compared to the lowest, and 2.6 times higher in the middle (pre-diabetic) group compared to the lowest.

The authors say: "This study shows, for the first time, that elevated FBG (?7.0 mmol/l) at admission is independently associated with increased 28-day mortality and percentages of in-hospital complications in COVID-19 patients without previous diagnosis of diabetes... we have also shown that FBG of 7.0 mmol/l or higher is associated with increased mortality, regardless of whether the patient has pneumonia that is more or less severe."

They add: "These results indicate that our study included both undiagnosed diabetic patients and non-diabetic patients with hyperglycaemia caused by an acute blood-glucose disorder, since the 29% found in the highest FBG group is much higher than the estimated prevalence of diabetes in the Chinese population at 12%. Similarly to what was found in a previous study, COVID-19 patients might suffer from high blood sugar brought about by other conditions, and critically ill patients may develop acute insulin resistance, manifested by high levels of blood sugar and insulin levels. Patients with conditions not related to diabetes, such as severe sepsis, systemic inflammatory response syndrome (SIRS) and traumatic brain injury tend to have abnormally high blood sugar."

The authors note several limitations with their study. First, this was a retrospective study. Second, they did not analyse glycated haemoglobin (HbA1c), a long-term blood sugar control indicator that helps distinguish patients with poor long-term blood sugar control from those with stress hyperglycaemia. Also, they did not have sufficient data to study the effect of glucose-lowering treatment (e.g. insulin, metformin) on the outcome of the patients in their study. However, they believe that acute hyperglycaemia is more important than long-term glycaemic control in predicting the prognosis of hospitalised COVID-19 patients.

The authors suggest that possible mechanisms for this increased mortality include hyperglycaemia-induced changes in coagulation (clotting), worsening of endothelial function (the function of the walls of blood vessels), and overproduction of inflammatory cytokines produced by the immune system (the so-called cytokine storm).

The authors conclude: "In conclusion, a fasting blood glucose level of 7.0 mmol/l or higher at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes. Blood sugar testing and control should be recommended to all COVID-19 patients even if they do not have pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders. During a pandemic of COVID-19, measuring fasting blood glucose can facilitate the assessment of prognosis and early intervention of hyperglycaemia to help improve the overall outcomes in treatment of COVID-19."

https://www.sciencedaily.com/releases/2020/07/200710212247.htm

Physicians give first comprehensive review of COVID-19's effects outside the lung

July 10, 2020

Science Daily/Columbia University Irving Medical Center

After only a few days caring for critically ill COVID-19 patients at the start of the outbreak in New York City, Aakriti Gupta, MD, realized that this was much more than a respiratory disease.

"I was on the front lines right from the beginning. I observed that patients were clotting a lot, they had high blood sugars even if they did not have diabetes, and many were experiencing injury to their hearts and kidneys," says Gupta, one of the first Columbia cardiology fellows to be deployed to the COVID intensive care units at Columbia University Irving Medical Center.

In early March, there wasn't much clinical guidance on the non-respiratory effects of COVID-19, so Gupta decided to coalesce findings from studies that were just beginning to appear in the literature with what the physicians were learning from experience.

Gupta, along with senior author Donald Landry, MD, PhD, chair of medicine at Columbia University Vagelos College of Physicians and Surgeons, organized senior co-authors, and Gupta, along with two other colleagues, Mahesh Madhavan, MD, a cardiology fellow at CUIMC, and Kartik Sehgal, MD, a hematology/oncology fellow at Beth Israel Deaconess Medical Center/Harvard Medical School, mobilized clinicians at Columbia, Harvard, Yale, and Mount Sinai Hospital, among other institutions, to review the latest findings on COVID-19's effect on organ systems outside the lungs and provide clinical guidance for physicians.

Their review -- the first extensive review of COVID-19's effects on all affected organs outside the lungs -- was published today in Nature Medicine.

"Physicians need to think of COVID-19 as a multisystem disease," Gupta says. "There's a lot of news about clotting but it's also important to understand that a substantial proportion of these patients suffer kidney, heart, and brain damage, and physicians need to treat those conditions along with the respiratory disease."

Blood Clots, Inflammation, and an Immune System in Overdrive

"In just the first few weeks of the pandemic, we were seeing a lot of thrombotic complications, more than what we would have anticipated from experience with other viral illnesses," says Sehgal, "and they can have profound consequences on the patient."

Scientists think these clotting complications may stem from the virus's attack on cells that line the blood vessels. When the virus attacks blood vessel cells, inflammation increases, and blood begins to form clots, big and small. These blood clots can travel all over the body and wreak havoc on organs, perpetuating a vicious cycle of thromboinflammation.

To combat clotting and its damaging effects, clinicians at Columbia, many of whom are co-authors on this review, are conducting a randomized clinical trial to investigate the optimal dose and timing of anticoagulation drugs in critically ill patients with COVID-19.

The untempered inflammation can also overstimulate the immune system, and though doctors initially shied away from using steroids to globally suppress the immune system, a recent clinical trial has found that at least one steroid, dexamethasone, reduced deaths in ventilated patients by one-third. Randomized clinical trials are underway to target specific components of thromboinflammation and the immune system, such as interleukin-6 signaling.

"Scientists all over the world are working at an unprecedented rate towards understanding how this virus specifically hijacks the normally protective biological mechanisms. We hope that this would help in the development of more effective, precise, and safer treatments for COVID-19 in the near future," says Sehgal.

Straight to the Heart

Clots can cause heart attacks, but the virus attacks the heart in other ways, one author says.

"The mechanism of heart damage is currently unclear, as the virus has not been frequently isolated from the heart tissue in autopsy cases," says Gupta.

The heart muscle may be damaged by systemic inflammation and the accompanying cytokine release, a flood of immune cells that normally clears up infected cells but can spiral out of control in severe COVID-19 cases.

Despite the degree of heart damage, physicians were not able to utilize the diagnostic and therapeutic strategies, including heart biopsies and cardiac catheterizations, that they would normally use during the early stages of the pandemic given the need to protect personnel and patients from viral transmission. This has changed as the disease prevalence has gone down in New York CIty.

Kidney Failure

Another surprising finding was the high proportion of COVID-19 patients in the ICU with acute kidney damage.

The ACE2 receptor used by the virus to gain entry into the cells is found in high concentrations in the kidney and could likely be responsible for the renal damage. Studies in China reported renal complications, but in New York City, clinicians saw renal failure in up to 50% of patients in the ICU.

"About 5 to 10% of patients needed dialysis. That's a very high number," Gupta says.

Data regarding long-term renal damage are currently lacking, but a significant proportion of patients will likely go on to require permanent dialysis.

"Future studies following patients who experienced complications during hospitalizations for COVID-19 will be crucial," notes Madhavan.

Neurological Effects

Neurological symptoms, including headache, dizziness, fatigue, and loss of smell, may occur in about a third of patients.

More concerning, strokes caused by blood clots occur in up to 6% of severe cases and delirium in 8% to 9%.

"COVID-19 patients can be intubated for two to three weeks; a quarter require ventilators for 30 or more days," Gupta says.

"These are very prolonged intubations, and patients need a lot of sedation. 'ICU delirium' was a well known condition before COVID, and the hallucinations may be less an effect of the virus and more an effect of the prolonged sedation."

"This virus is unusual and it's hard not to take a step back and not be impressed by how many manifestations it has on the human body," says Madhavan.

"Despite subspecialty training as internists, it's our job to keep all organ systems in mind when caring for the patients in front of us. We hope that our review, observations, and recommendations can help other clinicians where cases are now surging."

https://www.sciencedaily.com/releases/2020/07/200710212240.htm

Global COVID-19 registry finds strokes associated with COVID-19 are more severe, have worse outcomes and higher mortality

July 10, 2020

Science Daily/American Heart Association

Patients with COVID-19 who have an acute ischemic stroke (AIS) experience more severe strokes, have worse functional outcomes and are more likely to die of stroke than AIS patients who do not have COVID-19. The wide range of complications associated with COVID-19 likely explain the worse outcomes.

Acute ischemic strokes (AIS) associated with COVID-19 are more severe, lead to worse functional outcomes and are associated with higher mortality , according to new research published yesterday in Stroke, a journal of the American Stroke Association, a division of the American Heart Association.

In "Characteristics and Outcomes in Patients with COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry," researchers analyzed data on patients with COVID-19 and AIS treated at 28 health care centers in 16 countries this year and compared them to patients without COVID-19 from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) Registry, from 2003 to 2019. Researchers sought to determine the clinical characteristics and outcomes of patients with COVID-19 and AIS.

Between January 27, 2020 to May 19, 2020, there were 174 patients hospitalized with COVID-19 and AIS. Each COVID-19 patient with AIS was matched and compared to a non-COVID-19 AIS patient based on a set of pre-specified factors including age, gender and stroke risk factors (hypertension, diabetes, atrial fibrillation, coronary artery disease, heart failure, cancer, previous stroke, smoking, obesity and dyslipidemia). The final analysis included 330 patients total.

In both patient groups, stroke severity was estimated with the National Institute of Health Stroke Scale (NIHSS), and stroke outcome was assessed by the modified Rankin score (mRS). When AIS patients with COVID-19 were compared to non-COVID-19 patients:

• COVID-19 patients had more severe strokes (median NIHSS score of 10 vs. 6, respectively);

• COVID-19 patients had higher risk for severe disability following stroke (median mRS score 4 vs. 2, respectively); and

• COVID-19 patients were more likely to die of AIS.

The researchers noted there are several potential explanations for the relationship between COVID-19-associated strokes and increased stroke severity: "The increased stroke severity at admission in COVID-19-associated stroke patients compared to the non-COVID-19 cohort may explain the worse outcomes. The broad, multi-system complications of COVID-19, including acute respiratory distress syndrome, cardiac arrhythmias, acute cardiac injury, shock, pulmonary embolism, cytokine release syndrome and secondary infection, probably contribute further to the worse outcomes including higher mortality in these patients. ... The association highlights the urgent need for studies aiming to uncover the underlying mechanisms and is relevant for prehospital stroke awareness and in-hospital acute stroke pathways during the current and future pandemics."

https://www.sciencedaily.com/releases/2020/07/200710131516.htm

About half of health care workers positive for COVID-19 by serology have no symptoms

July 9, 2020

Science Daily/Vanderbilt University Medical Center

The IVY Research Network has completed initial studies evaluating the epidemiology of COVID-19 in health care workers and patients.

Among 249 front-line health care workers who cared for COVID-19 patients during the first month of the pandemic in Tennessee, 8% tested positive for COVID-19 antibodies by serology testing, suggesting they had contracted COVID-19 in the first several weeks of taking care of COVID-19 patients. Among these health care workers with positive serology results, 42% reported no symptoms of a respiratory illness in the prior two months. This suggests that front-line health care workers are at high risk for COVID-19 and that many health care workers with the virus may not have typical symptoms of a respiratory infection. These results were published in the journal Clinical Infectious Diseases on July 6.

"Our results suggest that screening health care workers for COVID-19 even when they don't have any symptoms could be important to prevent the spread of the virus within hospitals," said Wesley Self, MD, associate professor of Emergency Medicine at Vanderbilt University Medical Center and lead investigator for the IVY Network.

Investigator Bo Stubblefield, MD, instructor of Emergency Medicine, added, "We are continuing to study COVID-19 in front-line health care workers across the country to better understand what may be done to decrease their risk of infection, such as using specific types of personal protective equipment."

In a separate study, the IVY investigators studied 350 patients across 11 medical centers in the U.S. who tested positive for COVID-19; 54% of these patients reported no close contact with another person known to have COVID-19 in the two weeks before getting sick.

"With over half of COVID-19 patients not identifying a clear source of their infection, this study reinforces the need for practical measures to reduce the spread of the virus, such as social distancing and the use of face coverings when out in public," Self said.

Additionally, 40% of COVID-19 patients in the study remained symptomatic two weeks after a positive COVID-19 test, showing that patients with COVID-19 tend to remain ill longer than with other respiratory infections, such as influenza. The results were published by the journal Morbidity and Mortality Weekly Report on June 30.

The IVY Network is a collaborative research group of multiple medical centers in the U.S led by Vanderbilt University Medical Center. It is funded by Centers of Disease Control and Prevention (CDC) to conduct research on severe respiratory infections, including COVID-19 and influenza.

https://www.sciencedaily.com/releases/2020/07/200709113509.htm

Black individuals at higher risk for contracting COVID-19, according to new research

July 9, 2020

Science Daily/American Thoracic Society

Results of an analysis published in the Annals of the American Thoracic Society found that Black individuals were twice as likely as White individuals to test positive for COVID-19. The average age of all participants in the study was 46. However, those infected were on average 52 years old, compared to those who tested negative, who were 45 years old on average.

"Association of Black Race with Outcomes in COVID-19 Disease: A Retrospective Cohort Study" is not the first to examine race. However, it provides further evidence that, while anyone can get COVID-19, race is indeed a factor in the extent to which some populations are affected. Of the 4413 individuals tested, 17.8 percent tested positive. Of those who tested positive, 78.9 percent were Black while 9.6 percent were White.

Study author Ayodeji Adegunsoye, MD, MS, assistant professor of medicine at the University of Chicago, sees logic in the results of the analysis as it relates to the infection rates along racial lines: "I think this really amplifies how pre-existing socioeconomic and health care disparities affect outcomes in the population. We already know that the common comorbidities that have been associated with COVID such as hypertension and diabetes disproportionately affect the Black community. So, it wasn't too surprising that COVID-19 seemed to more commonly affect Black individuals as well."

In addition, noted Dr. Adegunsoye, given that Black individuals are overly represented in the service industry, and therefore more likely to be essential workers, their risk of exposure to COVID-19 is greater: "Even during precautionary lockdowns to reduce spread, these jobs were often deemed essential services, and included jobs such as bus drivers, janitors, city sanitation workers, hospital food production personnel, security guards, etc. so it wasn't too surprising that Black people were disproportionately infected and subsequently hospitalized with the virus."

The results showing that the individuals who tested positive were older than their counterparts who tested negative is consistent with reports of infection rates in the U.S. and elsewhere. "We have observed that for various reasons, older individuals are more likely to develop severe symptoms when they get infected and therefore they are more likely to get tested for COVID-19," said Dr. Adegunsoye.

"It's a vicious cycle of sorts, as older people are more likely to have hypertension and other comorbid diseases, which further increase the risk for hospitalization with COVID. Even after accounting for their older age, Black patients were still at significantly increased risk of COVID-19 infection and hospitalization."

In addressing the disparity in COVID-19 infection rates, Dr. Adegunsoye proposes making COVID-19 screening free and widely accessible. He hopes that there will be an increase in policy decisions that result in increased funding for community-led prevention efforts as well as "improved public enlightenment campaigns targeted at minorities to reduce the risk of developing hypertension and diabetes."

These measures, together with renewed strategic focus on reducing health inequities, will improve the lives of all Americans.

https://www.sciencedaily.com/releases/2020/07/200709085329.htm

Our itch to share helps spread COVID-19 misinformation

Study finds social media sharing affects news judgment, but a quick exercise reduces the problem

July 9, 2020

Science Daily/Massachusetts Institute of Technology

To stay current about the Covid-19 pandemic, people need to process health information when they read the news. Inevitably, that means people will be exposed to health misinformation, too, in the form of false content, often found online, about the illness.

Now a study co-authored by MIT scholars contains bad news and good news about Covid-19 misinformation -- and a new insight that may help reduce the problem.

The bad news is that when people are consuming news on social media, their inclination to share that news with others interferes with their ability to assess its accuracy. The study presented the same false news headlines about Covid-19 to two groups of people: One group was asked if they would share those stories on social media, and the other evaluated their accuracy. The participants were 32.4 percent more likely to say they would share the headlines than they were to say those headlines were accurate.

"There does appear to be a disconnect between accuracy judgments and sharing intentions," says MIT professor David Rand, co-author of a new paper detailing the findings. "People are much more discerning when you ask them to judge the accuracy, compared to when you ask them whether they would share something or not."

The good news: A little bit of reflection can go a long way. Participants who were more likely to think critically, or who had more scientific knowledge, were less likely to share misinformation. And when asked directly about accuracy, most participants did reasonably well at telling true news headlines from false ones.

Moreover, the study offers a solution for over-sharing: When participants were asked to rate the accuracy of a single non-Covid-19 story at the start of their news-viewing sessions, the quality of the Covid-19 news they shared increased significantly.

"The idea is, if you nudge them about accuracy at the outset, people are more likely to be thinking about the concept of accuracy when they later choose what to share. So then they take accuracy into account more when they make their sharing decisions," explains Rand, who is the Erwin H. Schell Associate Professor with joint appointments at the MIT Sloan School of Management and the Department of Brain and Cognitive Sciences.

The paper, "Fighting COVID-19 misinformation on social media: Experimental evidence for a scalable accuracy nudge intervention," appears in Psychological Science. Besides Rand, the authors are Gordon Pennycook, an assistant professor of behavioral science at the University of Regina; Jonathan McPhetres, a postdoc at MIT and the University of Regina who is starting a position in August as an assistant professor of psychology at Durham University; Yunhao Zhang, a PhD student at MIT Sloan; and Jackson G. Lu, the Mitsui Career Development Assistant Professor at MIT Sloan.

Thinking, fast and slow

To conduct the study, the researchers conducted two online experiments in March, with a total of roughly 1,700 U.S. participants between them, using the survey platform Lucid. Participants matched the nation's distribution of age, gender, ethnicity, and geographic region.

The first experiment had 853 participants, and used 15 true and 15 false news headlines about Covid-19, in the style of Facebook posts, with a headline, photo, and initial sentence from a story. The participants were split into two groups. One group was asked if the headlines were accurate; the second group was asked if they would consider sharing the posts on platforms such as Facebook and Twitter.

The first group correctly judged the stories' accuracy about two-thirds of the time. The second group might therefore be expected to share the stories at a similar rate. However, the participants in the second group shared about half of the true stories, and just under half of the false stories -- meaning their judgment about which stories to share was almost random in regard to accuracy.

The second study, with 856 participants, used the same group of headlines and again split the participants into two groups. The first group simply looked at the headlines and decided whether or not they would share them on social media.

But the second group of participants were asked to evaluate a non-Covid-19 headline before they made decisions about sharing the larger group of Covid-19 headlines. (Both studies were focused on headlines and the single sentence of text, since most people only read headlines on social media.) That extra step, of evaluating one non-Covid-19 headline, made a substantial difference. The "discernment" score of the second group -- the gap between the number of accurate and inaccurate stories they shared -- was almost three times larger than that of the first group.

The researchers evaluated additional factors that might explain tendencies in the responses of the participants. They gave all participants a six-item Cognitive Reflection Test (CRT), to evaluate their propensity to analyze information, rather than relying on gut instincts; evaluated how much scientific knowledge participants had; and looked at whether respondents were located close to Covid-19 outbreaks, among other things. They found that participants who scored higher on the CRT, and knew more about science, rated headlines more accurately and shared fewer false headlines.

Those findings suggest that the way people assess news stories has less to do with, say, preset partisan views about the news, and a bit more to do with their broader cognitive habits.

"A lot of people have a very cynical take on social media and our moment in history, that we're post-truth and no one cares about the truth any more," Pennycook says. "Our evidence suggests it's not that people don't care; it's more that they're distracted."

Something systemic about social media

The study follows others Rand and Pennycook have conducted about explicitly political news, which similarly suggest that cognitive habits, more so than partisan views, influence the way people judge the accuracy of news stories and lead to the sharing of misinformation. In this study, the scholars wanted to see if readers analyzed Covid-19 stories, and health information, differently than political information. But the results were generally similar to the political-news experiments the researchers have conducted.

"Our results suggest that the life-and-death stakes of Covid-19 do not make people suddenly take accuracy into [greater] account when they're deciding what to share," Lu says.

Indeed, Rand suggests, the very importance of Covid-19 as a subject may interfere with readers' ability to analyze it.

"Part of the issue with health and this pandemic is that it's very anxiety-inducing," Rand says. "Being emotionally aroused is another thing that makes you less likely to stop and think carefully."

Still, the central explanation, the scholars think, is simply the structure of social media, which encourages rapid browsing of news headlines, elevates splashy news items, and rewards users who post eye-catching news, by tending to give them more followers and retweets, even if those stories happen to be untrue.

"There is just something more systemic and fundamental about the social media context that distracts people from accuracy," Rand says. "I think part of it is that you're getting this instantaneous social feedback all the time. Every time you post something, you immediately get to see how many people liked it. And that really focuses your attention on: How many people are going to like this? Which is different from: How true is this?"

The research was supported by the Ethics and Governance of Artificial Intelligence Initiative of the Miami Foundation; the William and Flora Hewlett Foundation; the Omidyar Network; the John Templeton Foundation; the Canadian Institute of Health Research; and the Social Sciences and Humanities Research Council of Canada.

https://www.sciencedaily.com/releases/2020/07/200709121232.htm

Contracting COVID-19: lifestyle and social connections may play a role

July 9, 2020

Science Daily/Association for Psychological Science

Unhealthy lifestyle choices, like smoking and avoiding exercise, are known risk factors for certain cancers and cardiovascular disease. A growing body of research reveals that these risk factors and a lack of supportive social connections can also increase the risk of developing respiratory infections, like the common cold and influenza.

A new article published in the journal Perspectives on Psychological Science explores how lifestyle, social, and psychological factors also may increase the risk of contracting COVID-19.

"We know little about why some of the people exposed to the coronavirus that causes COVID-19 are more likely to develop the disease than others," said Sheldon Cohen, a professor of psychology at Carnegie Mellon University and one of the authors on the paper. "Our research on psychological factors that predict susceptibility to other respiratory viruses may provide clues to help identify factors that matter for COVID-19."

Through a series of studies spanning more than 30 years, Cohen and his team examined how lifestyle, social, and psychological factors affect whether or not healthy adults exposed to respiratory viruses become ill. This work focused on eight viral strains that cause the common cold and two that cause influenza.

"In our work, we intentionally exposed people to cold and influenza viruses and studied whether psychological and social factors predict how effective the immune system is in suppressing infection, or preventing or mitigating the severity of illness," said Cohen. "We found a strong correlation between social and psychological stressors and increased susceptibility."

Intriguingly, the researchers also found that social integration and social support offer a protective shield against respiratory infection and illness.

Until now, the only tactics to slow the spread of coronavirus have been behavioral changes that reduce the probability of being exposed to the virus, such as stay-at-home measures and social-distancing requirements. These same behaviors, however, are often associated with interpersonal stressors, like loneliness, loss of employment, and familial conflict. According to the researchers, these stressors may be powerful predictors of how a person will respond if exposed to coronavirus because of the stressors' direct physiological effects on immunity and their psychological factors, which are thought to have their influence through the mind-body connection.

Cohen's work demonstrates that psychological and social stressors are associated with an overproduction of proinflammatory chemicals known as cytokines in response to cold and influenza viruses. In turn, this excess of inflammation was associated with an increased risk of becoming ill.

Similarly, research on COVID-19 has shown that producing an excess of proinflammatory cytokines is associated with more severe COVID-19 infections, suggesting that a stress-triggered excessive cytokine response might also contribute to excessive inflammation and symptoms in COVID-19 patients.

Cohen and his colleagues acknowledge that, as of now, there are no firmly established links between behavioral and psychological factors and the risk for disease and death in persons exposed to the corona virus that causes COVID-19. However, their prior body of research may be relevant to the current pandemic because, they note, the most potent predictors of disease, interpersonal and economic stressors, are the types of stressors that are commonly experienced among those who are isolated or in quarantine.

"If you have a diverse social network (social integration), you tend to take better care of yourself (no smoking, moderate drinking, more sleep and exercise)," said Cohen. "Also if people perceive that those in their social network will help them during a period of stress or adversity (social support) then it attenuates the effect of the stressor and is less impactful on their health."

https://www.sciencedaily.com/releases/2020/07/200709113521.htm

Distorted passage of time during the COVID-19 lockdown

Survey results suggest people in United Kingdom perceived time passing differently compared to pre-lockdown

July 9, 2020

Science Daily/PLOS

A survey conducted in the U.K. suggests that social and physical distancing measures put in place during the Covid-19 pandemic significantly impacted people's perception of how quickly time passed compared to their pre-lockdown perceptions. Ruth S. Ogden of Liverpool John Moores University, U.K., presented these findings in the open-access journal PLOS ONE on July 6, 2020.

Previous research suggests that one's perception of how quickly time passes can vary according to one's emotions, the number of daily tasks one must perform, and other factors. However, most of that research has been limited to normal day-to-day life. Social and physical distancing measures put in place during the Covid-19 pandemic provide a unique opportunity to examine how significant changes to life's daily routine impact time perception.

Ogden prepared an online questionnaire asking participants to rate on a sliding scale how quickly they felt time was passing compared to normal, both over the course of a single day and over a full week. The questionnaire also evaluated people's emotional state, task load, and satisfaction with levels of social interaction. The final analysis included 604 participants in the U.K. who answered the questionnaire between April 7 and April 30, 2020.

Ogden found that more than 80 percent of participants experienced changes to how quickly they perceived time passing during lockdown compared to pre-lockdown. Those who were older or less satisfied with their current levels of social interaction were more likely to experience slower passage of time over the course of a day or week. Slower passage of time over the course of a day was also associated with higher stress and a lower task load.

These findings suggest that significant changes to life's daily routine distort perception of time. Future research could look deeper into the effects of specific factors, such as whether social satisfaction influences perception of time during normal daily life, or if its significance in this study is due to the unique social impacts of the Covid-19 lockdown.

Author Ruth Ogden notes: "80% of people experienced distortion to the passage of time during the lockdown. Lockdown passing more slowly than normal was associated with older age and reduced satisfaction with social interactions."

https://www.sciencedaily.com/releases/2020/07/200709105230.htm

Lung, immune function in kids could protect from severe COVID-19

July 8, 2020

Science Daily/University of Texas Health Science Center at Houston

Differences in lung physiology and immune function in children could be why they are more often spared from severe illness associated with COVID-19 than adults, according to pediatric and adult physicians at The University of Texas Health Science Center at Houston (UTHealth) and Baylor College of Medicine, who teamed up to investigate the disparity.

The perspectives paper was recently published in American Journal of Physiology-Lung Cellular and Molecular Physiology.

According to the paper, only about 1.7% of the first 149,082 cases in the U.S. were infants, children, and adolescents younger than 18 years old. Authors noted that children under 18 make up 22% of the U.S. population. Only three pediatric deaths were identified by the Centers for Disease Control and Prevention (CDC) as of April 2020.

"These profoundly decreased rates of symptomatic infection, hospitalization, and death are well beyond statistical significance, require further examination, and may hold the key to identifying therapeutic agents," the authors wrote.

Angiotensin-converting enzyme 2s, called ACE2, are the doors that allow SARS-CoV-2, the novel coronavirus that causes COVID-19, to enter the body's cells. Children naturally have less ACE2 in the lungs than adults.

"ACE2 are important for viral entry and there seems to be less of them in children, because they increase with age," said Matthew Harting, MD, MS, assistant professor in the Department of Pediatric Surgery at McGovern Medical School at UTHealth, pediatric surgeon with UT Physicians, and senior author of the paper. Harting is also director of the pediatric ECMO program providing advanced cardiac and respiratory support at Children's Memorial Hermann Hospital.

In addition to fewer ACE2 receptors, the authors note the immune system in children responds to viruses differently than that of adults, leaving less opportunity for severe illness in pediatric patients. There are several different mechanisms behind the differences, including the retention of T-cells in children, which are able to fight off or limit inflammation.

"T-cells have a viral response and also an immune modulator response. In severe cases of adult COVID-19 patients, we've seen that those T-cells are reduced, so the ability to fight the virus is also reduced. In kids, those T-cells seem to be maintained, so they are still able to prevent the virus," said Harry Karmouty-Quintana, PhD, an assistant professor in the Department of Biochemistry and Molecular Biology at McGovern Medical School, and a co-author of the paper.

Lung tissue in children naturally has a higher concentration of regulator T-cells. Patients with higher levels of T-cells also have higher levels of Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor, an anti-inflammatory cytokine.

"IL-10 inhibits the inflammation of other components like IL-6 that are detrimental. Adults tend to experience hyperinflammatory state, where kids do not," Karmouty-Quintana said. "In preclinical studies in mice, IL-10 has also shown to decrease with age."

The paper's findings were made possible through collaboration in a multidisciplinary group made up of pediatric and adult physicians and scientists in pediatric surgery, adult critical care, neonatology, and molecular biology.

"We, as physicians, have been challenged with the question of how to treat COVID-19 and we're learning in real time," said Bindu Akkanti, MD, associate professor of critical care medicine with McGovern Medical School, attending physician in critical care with Memorial Hermann-Texas Medical Center, and a study co-author. "I knew that to figure out the best way to treat adults, we needed to get a team together to get to the bottom of why children were being spared from severe illness related to the virus. So, I reached out to Dr. Karmouty-Quintana and we teamed up with Dr. Harting and two other physicians in the Texas Medical Center to start investigating." Akkanti also sees pulmonary patients at UT Physicians.

"Collaborations like this between adult and pediatric providers are really important and this disease highlights where we can learn a lot when we compare the way it behaves in younger kids with older people," Harting said. "Even now as we're learning about effective treatments, we're seeing younger people handle this disease better than older people. Moving forward, physicians and scientists need multidisciplinary collaboration to continue learning -- this is just another step in the right direction to attack this virus."

Krithika Lingappan, MBBS, was the first author of the paper and Jonathan Davies, MD, was a co-author. Both Lingappan and Davies are assistant professors of pediatrics at Baylor College of Medicine and neonatologists with Texas Children's Hospital.

As a result of the collaboration, the team has begun a new study using blood samples from patients in different stages of COVID-19 to continue to understand how to treat the virus and the disparities in disease progression between children and adults.

https://www.sciencedaily.com/releases/2020/07/200708155528.htm

Researchers propose novel approach to limit organ damage for patients with severe COVID-19

July 8, 2020

Science Daily/Beth Israel Deaconess Medical Center

Patients with severe COVID-19 frequently experience a life-threatening immune reaction, sometimes called a cytokine storm, which can lead to respiratory failure, organ damage and potentially death. With no FDA-approved treatment currently available for SARS-CoV-2, the virus that causes COVID-19, researchers are racing to find ways to stop the virus or the inflammatory overreaction it provokes in its tracks.

In a paper published in Cancer and Metastasis Reviews and selected by the journal as the featured publication, a team of researchers from Beth Israel Deaconess Medical Center and Brigham and Women's Hospital propose that controlling the local and systemic inflammatory response in COVID-19 may be as important as anti-viral and other therapies.

Led by Dipak Panigrahy, MD, of the Cancer Center at BIDMC, and Charles N. Serhan, PhD, DSc, director of the Center of Experimental Therapeutics and a member of the Department of Anesthesiology, Perioperative and Pain Medicine at Brigham and Women's Hospital, the researchers suggest that a family of molecules naturally produced by the human body may be harnessed to resolve inflammation in patients with severe COVID-19, thereby reducing the acute respiratory distress and other life-threatening complications associated with the viral infection.

"Controlling the body's inflammatory response is key to the management of COVID-19 and may be as important to managing the pandemic as anti-viral therapies or a vaccine," Panigrahy said. "Our team proposes using molecules made by the body called pro-resolution lipid mediators -- which are currently in clinical trials for other inflammatory diseases -- as a novel approach to turning off the inflammation and preventing the cytokine storm caused by COVID-19."

Cytokines are released by the body as part of its normal immune response to injured or infected tissues. Typically, the body also releases chemicals to put an end to -- or resolve -- the inflammatory response. But in a significant percentage of patients with severe COVID-19, the cytokines unleashed to kill the virus also do damage to infected lung cells. In turn, this injury to the lung tissues triggers additional inflammation, and the so-called "cytokine storm" begins to spiral out of control.

Naturally occurring molecules called resolvins -- discovered by Serhan and colleagues at BWH in 2002 -- actively turn off inflammation. Panigrahy, Serhan and colleagues have previously demonstrated that resolvins and related pro-resolution molecules could play a role in preventing cancer metastasis and progression. This class of molecules are also currently in clinical trials investigating their use against other inflammatory diseases, such as ocular, periodontal, and inflammatory bowel disease. Now, the scientists suggest, they could be re-deployed for the management of COVID-19.

"A paradigm shift is emerging in our understanding of the resolution of inflammation as an active biochemical process," said Serhan. "Activating the body's own resolution pathways with the use of resolvins and related pro-resolution molecules -- which, importantly, promote blog clot removal -- may complement current treatment strategies while limiting severe organ damage and improving outcomes in COVID-19 patients."

https://www.sciencedaily.com/releases/2020/07/200708135950.htm

The best (and worst) materials for masks

People making homemade masks might want to reach for a vacuum cleaner filter

July 8, 2020

Science Daily/University of Arizona

It's intuitive and scientifically shown that wearing a face covering can help reduce the spread of the novel coronavirus that causes COVID-19. But not all masks are created equal, according to new University of Arizona-led research.

Amanda Wilson, an environmental health sciences doctoral candidate in the Department of Community, Environment and Policy in the Mel and Enid Zuckerman College of Public Health, is lead author on a recent study published in the Journal of Hospital Infection that assessed the ability of a variety of nontraditional mask materials to protect a person from infection after 30 seconds and after 20 minutes of exposure in a highly contaminated environment.

When the researchers compared wearing masks to wearing no protection during 20-minute and 30-second exposures to the virus, they found that infection risks were reduced by 24-94% or by 44-99% depending on the mask and exposure duration. Risk reduction decreased as exposure duration increased, they found.

"N99 masks, which are even more efficient at filtering airborne particles than N95 masks, are obviously one of the best options for blocking the virus, as they can reduce average risk by 94-99% for 20-minute and 30-second exposures, but they can be hard to come by, and there are ethical considerations such as leaving those available for medical professionals," Wilson said.

The next best options, according to the research, are N95 and surgical masks and, perhaps surprisingly, vacuum cleaner filters, which can be inserted into filter pockets in cloth masks. The vacuum filters reduced infection risk by 83% for a 30-second exposure and 58% for a 20-minute exposure. Of the other nontraditional materials evaluated by the researchers, tea towels, cotton-blend fabrics and antimicrobial pillowcases were the next best for protection.

Scarves, which reduced infection risk by 44% after 30 seconds and 24% after 20 minutes, and similarly effective cotton t-shirts are only slightly better than wearing no mask at all, they found.

"We knew that masks work, but we wanted to know how well and compare different materials' effects on health outcomes," said Wilson, who specializes in quantitative microbial risk assessment.

Wilson and her team collected data from various studies of mask efficacy and created a computer model to simulate infection risk, taking various factors into consideration.

"One big component of risk is how long you're exposed. We compared risk of infection at both 30 seconds and 20 minutes in a highly contaminated environment," she said.

Other conditions that impact risk of infection are the number of people around you and their distance from you, she said.

The size of virus-transporting droplets from sneezes, coughs or even speech is also a very important factor. Larger, heavier droplets carrying the virus drop out of the air faster than smaller, lighter ones. That's one reason distance helps reduce exposure.

"Aerosol size can also be affected by humidity," Wilson said. "If the air is drier, then aerosols become smaller faster. If humidity is higher, then aerosols will stay larger for a longer period of time, dropping out faster. That might sound good at first, but then those aerosols fall on surfaces, and that object becomes another potential exposure route."

The study also showed that the more time a person spends in an environment where the virus is present, the less effective a mask becomes.

"That doesn't mean take your mask off after 20 minutes," Wilson said, "but it does mean that a mask can't reduce your risk to zero. Don't go to a bar for four hours and think you're risk free because you're wearing a mask. Stay home as much as possible, wash your hands often, wear a mask when you're out and don't touch your face."

Masks protect the wearer and others in a number of different ways. Wilson said there are two "intuitive ways" that masks filter larger aerosols: mechanical interception and inertial impaction.

"The denser the fibers of a material, the better it is at filtering. That's why higher thread counts lead to higher efficacy. There's just more to block the virus," she said. "But some masks (such as those made from silk) also have electrostatic properties, which can attract smaller particles and keep them from passing through the mask as well."

The model developed by Wilson and her colleagues included parameters such as inhalation rate -- the volume of air inhaled over time -- and virus concentration in the air.

"We took a lot of research data, put it into a mathematical model and related those data points to each other," Wilson said. "For example, if we know people's inhalation rates vary by this much and know this much virus is in the air and these materials offer this much efficiency in terms of filtration, what does that mean for infection risk? We provide a range, in part, because everyone is different, such as in how much air we breathe over time."

Wilson also said it's important for a mask to have a good seal that pinches at nose, and she noted that people shouldn't wear a mask beneath the nose or tuck it under the chin when not in use.

"Proper use of masks is so important," Wilson said. "Also, we were focusing on masks protecting the wearer, but they're most important to protect others around you if you're infected. If you put less virus out into the air, you're creating a less contaminated environment around you. As our model shows, the amount of infectious virus you're exposed to has a big impact on your infection risk and the potential for others' masks to protect them as well."

https://www.sciencedaily.com/releases/2020/07/200708125350.htm

COVID-19 brain complications found across the globe

July 8, 2020

Science Daily/University of Liverpool

Cases of brain complications linked to COVID-19 are occurring across the globe, a new review by University of Liverpool researchers has shown.

Published in The Lancet Neurology, the study found that strokes, delirium and other neurological complications are reported from most countries where there have been large outbreaks of the disease.

COVID-19 has been associated mostly with problems like difficulty breathing, fever and cough. However, as the pandemic has continued, it has become increasingly clear that other problems can occur in patients. These include confusion, stroke, inflammation of the brain, spinal cord, and other kinds of nerve disease.

A recent Liverpool-led study of COVID-19 patients hospitalised in the UK found a range of neurological and psychiatric complications that may be linked to the disease.

To get a sense of the wider picture, the researchers brought together and analysed findings from COVID-19 studies across the globe that reported on neurological complications. The review, which included studies from China, Italy and the USA among others, found almost 1000 patients with COVID-19-associated brain, spinal cord and nerve disease.

Research Fellow, Dr Suzannah Lant, who was working on the project, said: "Whilst these complications are relatively uncommon, the huge numbers of COVID-19 cases globally mean the overall number of patients with neurological problems is likely to be quite large."

One of the complications found to be linked to COVID-19 is encephalitis, which is inflammation and swelling of the brain.

Dr Ava Easton, CEO of the Encephalitis Society, and co-author on the paper said: "It is really important that doctors around the world recognise that COVID-19 can cause encephalitis and other brain problems, which often have potentially devastating, life-changing consequences for patients."

Professor Tom Solomon, senior author on the paper and Director of the Global COVID-Neuro Network, added: "Although such patients are being seen everywhere the virus occurs, many of the reports are lacking in detail. We are currently pooling data from individual patients all around the world, so that we can get a more complete picture. Doctors who would like to contribute patients to this analysis can contact us via the Global COVID-Neuro Network website."

For more information about the Global COVID-Neuro Network please visit https://braininfectionsglobal.tghn.org/covid-neuro-network/

https://www.sciencedaily.com/releases/2020/07/200708150550.htm

Study explains potential causes for 'happy hypoxia' condition in COVID-19 patients

Findings could prevent unnecessary intubation

July 8, 2020

Science Daily/Loyola University Health System

A new research study provides possible explanations for COVID-19 patients who present with extremely low, otherwise life-threatening levels of oxygen, but no signs of dyspnea (difficulty breathing). This new understanding of the condition, known as silent hypoxemia or "happy hypoxia," could prevent unnecessary intubation and ventilation in patients during the current and expected second wave of coronavirus.

The condition "is especially bewildering to physicians as it defies basic biology," said Martin J. Tobin, MD, Loyola Medicine and Edward J. Hines Jr. VA Hospital pulmonologist and critical care specialist, and professor, Loyola University Chicago Stritch School of Medicine. Dr. Tobin is lead author of the study, "Why COVID-19 Silent Hypoxemia is Baffling to Physicians," appearing recently in the online American Journal of Respiratory and Critical Care Medicine.

"In some instances, the patient is comfortable and using a phone at a point when the physician is about to insert a breathing (endotracheal) tube and connect the patient to a mechanical ventilator," said Dr. Tobin, "which while potentially lifesaving carries its own set of risks."

The study included 16 COVID-19 patients with very low levels of oxygen (as low as 50%; normal blood oxygen saturation is between 95 and 100%), without shortness of breath or dyspnea, and found that "several pathophysiological mechanisms account for most, if not all, cases of silent hypoxemia. This includes the initial assessment of a patient's oxygen level with a pulse oximeter.

"While a pulse oximeter is remarkably accurate when oxygen readings are high, it markedly exaggerates the severity of low levels of oxygen when readings are low," said Dr. Tobin. "Another factor is how the brain responds to low levels of oxygen. As oxygen levels drop in patients with COVID-19, the brain does not respond until oxygen falls to very low levels -- at which point a patient typically becomes short of breath," he said.

In addition, more than half of the patients had low levels of carbon dioxide, which may diminish the impact of an extremely low oxygen level.

"It is also possible that the coronavirus is exerting a peculiar action on how the body senses low levels of oxygen," said Dr. Tobin, which could be linked to the lack of smell, experienced by two-thirds of COVID-19 patients.

While acknowledging that further research is needed, the study concludes that "features about COVID-19 that physicians find baffling become less strange when viewed in the light of long-established principles of respiratory physiology."

"This new information may help to avoid unnecessary endotracheal intubation and mechanical ventilation, which presents risks, when the ongoing and much anticipated second wave of COVID-19 emerges," said Dr. Tobin.

https://www.sciencedaily.com/releases/2020/07/200702144732.htm

Men and younger adults less active in lockdown

Study finds women and older adults are most likely to meet exercise targets

July 7, 2020

Science Daily/Anglia Ruskin University

New research published in the journal BMJ Open Sport and Exercise Medicine indicates that men and younger adults have been less physically active during the COVID-19 lockdown.

The study, led by Anglia Ruskin University (ARU) and Ulster University, includes data from 911 UK adults who took part in an online survey which began on 17 March.

The research found that 75% of UK adults met the World Health Organisation's physical activity recommendations of 150 minutes of moderate physical activity or 75 minutes of vigorous physical activity per week, since the introduction of social distancing regulations.

This is higher than previous studies carried out before the COVID-19 pandemic, which found that between 58% and 66% of the UK adult population typically meet physical activity guidelines

The new study found that women, older adults, and those with a higher annual household income were significantly more likely to meet the WHO's physical activity guidelines. This is the opposite of studies carried out prior to the pandemic, where men and younger adults were found to have higher levels of physical activity.

Lead author Dr Lee Smith, Reader in Physical Activity and Public Health at Anglia Ruskin University (ARU), said: "The overall levels of physical activity are higher than we were expecting.

"It may be that the UK public have experienced an increase in free time and used this time to be physically active. Additionally, during the early stages of the outbreak, one of the few reasons to leave home was to take part in an hour of exercise. As well as offering a reason to go outside, this may have served as a target for some people.

"Typically, the proportion of UK adults meeting physical activity guidelines declines with age. Therefore, there should be additional support offered to older adults to encourage them to sustain this level of physical activity post pandemic."

https://www.sciencedaily.com/releases/2020/07/200707183930.htm

COVID-related discrimination disproportionately impacts racial minorities

Discrimination against people perceived to have COVID-19 increased from March to April 2020

July 7, 2020

Science Daily/University of Southern California

Discrimination against people thought to be infected with coronavirus was experienced by a rising number of United States residents, particularly racial minorities, in the early stages of the COVID-19 pandemic, according to a new study from the USC Dornsife College of Letters, Arts and Sciences.

From March to April 2020, the overall percentage of U.S. residents who experienced COVID-related discrimination more than doubled from 4% to 10%, according to researchers. The sharpest increase was among Asians and African Americans, who were most likely to report experiences of discrimination based on the perception they were infected with COVID-19.

In March, during the early stage of the pandemic in the U.S., 11% of Asians and 9% of African Americans had experienced discrimination by someone who perceived them as having the coronavirus, compared to 4% of whites. In April, this increased to 16% of Asians and 15% of African Americans, compared to 9% of whites, according to the study, which was published in the American Journal of Preventive Medicine.

Researchers analyzed responses from the Understanding Coronavirus in America tracking survey conducted by the USC Dornsife Center for Economic and Social Research (CESR) to evaluate the contribution of various risk factors for discrimination -- including race/ethnicity and wearing a face mask -- during in-person and social media encounters when discriminatory acts might occur. They also looked at how such discrimination was related to mental distress among U.S. adults in the early stage of the COVID-19 pandemic in March and April 2020.

Mask-wearing was a risk factor for discrimination

Survey participants consisted of a probability-based, nationally representative sample of 3,665 U.S. residents aged 18 years or older who completed COVID-19-related surveys online in March and April. To measure incidents of discrimination, respondents were asked if "people thinking they might have the coronavirus" acted as if they were afraid of them, threatened or harassed them, treated them with less courtesy and respect, or gave them poorer service at restaurants or stores.

"The early spike in the percentage of people who experienced COVID-related discrimination was attributable -- in part -- to discriminatory reactions to the growing number of people wearing masks or face coverings at the early stage of the pandemic," said Ying Liu, a research scientist with CESR.

The researchers found Asian Americans were the first racial/ethnic group to experience substantial discrimination, followed by African Americans, and that the higher degree of discrimination experienced by Asians in March was partially explained by their immigration status and mask-wearing.

African Americans' risk of experiencing discrimination was higher than other non-Asian groups and also increased faster between March and April than other groups, according to the study.

"This increase may in part be attributable to the spike in media coverage we saw during this time regarding African Americans' disproportionate vulnerability to COVID-19," said Kyla Thomas, a sociologist at CESR.

Mask-wearing was a persistent risk factor for discrimination associated with COVID-19, although it varied from March to April. The study found other groups, including frontline workers who didn't wear masks, people who worked partially or fully from home, and those who did not work experienced less discrimination.

"In March, before widespread stay-at-home orders and when mask-wearing was rare, people wearing masks were more likely to experience discrimination," said Brian Karl Finch, research professor of sociology and spatial sciences with CESR. "In April, only the frontline workers who wore masks had higher risks of experiencing discrimination."

The research team found that in some earlier weeks of the pandemic, people who were heavy users of social media were more likely to report an experience of discrimination. They also found that experiences of discrimination were associated with increased anxiety and depression, consistent with literature associating general discrimination with poorer mental health especially among racial/ethnic minorities.

"The relationship between COVID-related discrimination and worsening anxiety and depression is particularly pertinent during this pandemic, as it compounds mental health distress attributable to concerns of disease spread, social restrictions, and financial stress," said PhuongThao Le, a postdoctoral researcher at Johns Hopkins Bloomberg School of Public Health.

Stigma can undermine public health efforts

Discrimination toward people who share social or behavioral characteristics with COVID-19 patients, but may not carry the novel virus, was first seen in heightened anti-Chinese rhetoric online. Social media analyses showed a nearly 10-fold increase in the use of offensive language, and reports on in-person racist acts against Asians increased during the early stages of the pandemic.

"In mid-March, President Donald Trump referred to a 'China virus' or 'Chinese virus,' which coincided with an increase of online and in-person crimes including robbery and harassment of Asian Americans," said Savannah Brenneke, a pre-doctoral researcher at Johns Hopkins Bloomberg School of Public Health.

Researchers say this disease-associated stigma toward people, regardless of infection status, has been observed in previous outbreaks of novel viruses. For example, Mexicans and other Latinos were shunned during the 2009 H1N1 pandemic owing to the virus' link to hog farms where migrants worked.

The United Nations and the U.S. Centers for Disease Control and Prevention have called for increased attention to preventing stigma associated with COVID-19, which could undermine disease control efforts, worsen mental health outcomes and exacerbate disparities.

About the study

The UAS coronavirus surveys referred in this paper were initiated and financed by USC and funded in part by the Bill & Melinda Gates Foundation. The parent study protocol was approved by the USC IRB, and data access was granted by UAS' data user agreement.

Ms. Brenneke's work was supported by the National Institute on Drug Abuse (T32DA007292) and Dr. Le's work was supported by a training grant from the National Institute of Mental Health (T32MH103210).

The Understanding Coronavirus in America Study regularly surveys a panel of more than 7,000 people throughout the country to learn how COVID-19 impacts their attitudes, lives and behaviors. Data from the study, supported in part by the Bill & Melinda Gates Foundation and USC, is updated daily and available to researchers and the public at: covid19pulse.usc.edu.

https://www.sciencedaily.com/releases/2020/07/200707113208.htm

Lack of lockdown increased COVID-19 deaths in Sweden

July 6, 2020

Science Daily/University of Virginia Health System

Sweden's controversial decision not to lock down during COVID-19 produced more deaths and greater healthcare demand than seen in countries with earlier, more stringent interventions, a new analysis finds. But Sweden fared better than would be expected from its public-health mandates alone, roughly similar to France, Italy and Spain -- countries that had more stringent measures but adopted them after the pandemic took hold there.

Sweden's unusual approach also saw fewer patients admitted to intensive-care units than expected. But the country has seen a higher percentage of deaths in older patients outside ICUs than other countries when ICU beds were not limited. That suggests health authorities there have considered patients' chances of recovery in deciding who receives access to intensive care, the researchers say.

"Our study shows that individually driven infection-control measures can have a substantial effect on national outcomes, and we see Sweden as a good example of this case," said Peter Kasson, MD, PhD, of the University of Virginia School of Medicine and Sweden's Uppsala University. "Higher levels of individual action would further suppress the infection, while a complete lack of individual action would likely have led to runaway infection, which fortunately hasn't happened."

Understanding the Impact of COVID-19

Kasson and Uppsala's Lynn Kamerlin set out to analyze the effects of the country's public-health response using population, employment and household data. They say the insights gained from their work can guide future public-health policies. In particular, the findings will help doctors understand the effects of individual compliance with infection-control measures.

The researchers conclude that Sweden's "mild" government restrictions, coupled with a population willing to voluntarily self-isolate, produced results quite similar to those seen in countries that enacted more stringent measures later in the pandemic.

Sweden's per capita death rate was 35 per 100,000 as of May 15. Meanwhile, Denmark's death rate was 9.3 per 100,000, Finland's 5.2 and Norway's 4.7. All three neighboring countries enacted stricter policies. For comparison, the United States had 24 deaths per 100,000 as of May 15. But Sweden has fared better than hard-hit countries such as the United Kingdom and Spain.

"Sweden is perhaps the most prominent example of mitigation -- limiting the extent of socially and economically disruptive interventions while still aiming to slow spread and allow for an effective medical response," the researchers wrote in a new paper outlining their findings. "Studying the effects of this strategy, which elements are key to reducing mortality and healthcare need, and how it might compare to other approaches, is thus of critical importance to the global understanding of pandemic responses."

Key Measures in Sweden

While it did not opt for full lockdown, Sweden took several steps to mitigate the spread of COVID-19. The researchers created computer models to measure the effects of these steps, including voluntary self-isolation by symptomatic people and those over 70, closing schools and other interventions. They then validated their results by comparing the models with Sweden's death rate and compared Sweden's results to other countries'.

The researchers' models anticipated that Sweden's public-health mandates would result in 40 times more patients needing ICU beds than the number of ICU beds available before the pandemic. Voluntary self-isolation reduced this to five-fold, and the country essentially doubled its number of ICU beds as the pandemic emerged.

That still leaves many patients without a bed, however, and yet the country's ICUs weren't overrun. That outcome -- and the fact older patients in Sweden were several times more likely to die than to be admitted to an ICU -- prompted the researchers to analyze choices that Swedish health authorities made about who would receive intensive care.

"Analyzed by categorical age group, older Swedish patients with confirmed COVID-19 were more likely to die than to be admitted to the ICU, suggesting that predicted prognosis may have been a factor in ICU admission," the researchers wrote. "This likely reduced ICU load at the cost of more high-risk patients dying outside the ICU."

"The key finding is that individual actions matter," Kasson said. "If enough individuals stay home and take precautions when in the community, it can really change the infection curve. And we can't let up now."

Analysis Published

The researchers have published their analysis in the scientific journal Clinical Infectious Diseases. Kasson and Kamerlin collaborate at Uppsala University, and Kasson is part of UVA's Department of Molecular Physiology and Biological Physics. He also holds an appointment in the Department of Biomedical Engineering, a collaboration of UVA's School of Medicine and School of Engineering.

https://www.sciencedaily.com/releases/2020/07/200706100812.htm

Clinicians find encouraging results from functional MRI in an unresponsive patient with COVID-19

July 6, 2020

Science Daily/Massachusetts General Hospital

A patient with severe COVID-19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated functionally intact brain connections and later recovered the ability to follow commands

Many patients with severe coronavirus disease 2019 (COVID-19) remain unresponsive after surviving critical illness. Investigators led by a team at Massachusetts General Hospital (MGH) now describe a patient with severe COVID-19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated functionally intact brain connections and weeks later he recovered the ability to follow commands. The case, which is published in the Annals of Neurology, suggests that unresponsive patients with COVID-19 may have a better chance of recovery than expected.

In addition to performing standard brain imaging tests, the team took images of the patient's brain with a technique called resting-state functional magnetic resonance imaging (rs-fMRI), which evaluates the connectivity of brain networks by measuring spontaneous oscillations of brain activity. The patient was a 47-year-old man who developed progressive respiratory failure, and despite intensive treatment, he fluctuated between coma and a minimally conscious state for several weeks.

Standard brain imaging tests revealed considerable damage, but unexpectedly, rs-fMRI revealed robust functional connectivity within the default mode network (DMN), which is a brain network thought to be involved in human consciousness. Studies have shown that stronger DMN connectivity in patients with disorders of consciousness predicts better neurologic recovery. The patient's DMN connectively was comparable to that seen in healthy individuals, suggesting that the neurologic prognosis may not be as grim as conventional tests implied.

Twenty days later, on hospital day 61, the patient began following verbal commands. He blinked his eyes to command, opened his mouth to command, and on day 66 followed four out of four vocalization commands. By this time, he also consistently demonstrated gaze tracking with his eyes in response to visual and auditory stimuli.

"Because there are so many unanswered questions about the potential for recovery in unresponsive patients who have survived severe COVID-19, any available data that could inform prognosis are critical," said senior author Brian Edlow, MD, director of the Laboratory for NeuroImaging of Coma and Consciousness and associate director of the Center for Neurotechnology and Neurorecovery at MGH. "Our unexpected observations do not prove that functional MRI predicts outcomes in these patients, but they suggest that clinicians should consider the possibility that unresponsive survivors of severe COVID-19 may have intact brain networks. We should thus exercise caution before presuming a poor neurologic outcome based on our conventional tests."

Providing families with an accurate prognosis about neurological recovery is particularly challenging for patients with COVID-19, because so little is known about how the brain is affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or associated inflammation and clotting disorders. "Initially, our goal in the intensive care unit was to support patients through the critical illness of COVID-19," said lead author David Fischer, MD, Neurocritical Care fellow at MGH. "However, we found that a subset of patients, after surviving the critical illness, were not waking up as expected. As neurologists, we were asked by many families whether their loved ones would regain consciousness -- a critical question given that decisions about life support often hinged on the answer -- but we were uncertain. We used functional MRI to try to provide a more comprehensive assessment of brain function."

The application of functional MRI to critically ill patients with disorders of consciousness is the culmination of decades of work to develop this technology and ultimately translate it to clinical care. Co-author Bruce Rosen, MD, PhD, director of the Athinoula A. Martinos Center for Biomedical Imaging at MGH, and one of the developers of functional MRI in the early 1990s, explained that "we have to be cautious when interpreting results from a single patient, but this study provides proof of principle that clinicians may be able to use advanced imaging techniques like functional MRI to get a clearer picture of a patient's brain function, and hence the potential for recovery."

To facilitate dissemination of this tool to other hospitals around the world caring for patients with COVID-19, the investigators release the functional MRI sequence parameters and the data analysis pipeline at http://www.github.com/ComaRecoveryLab/COVID-19_rsfMRI.

https://www.sciencedaily.com/releases/2020/07/200706145437.htm

Individuals physically distanced before state mandates, slowing COVID-19 spread

July 2, 2020

Science Daily/Johns Hopkins University

Residents in all 25 of the U.S. counties hardest hit by COVID-19 began to limit their public movements six to 29 days before states implemented stay-at-home orders, according to Johns Hopkins University researchers.

The decline in the number of daily trips people made as tracked by mobile phone data helped slow the spread of the virus, according to findings published today in The Lancet Infectious Diseases journal from the Johns Hopkins team that created the world-famous online coronavirus tracking map.

"Our results strongly support the conclusion that social distancing played a crucial role in the reduction of case growth rates in multiple U.S. counties during March and April, and is therefore an effective mitigation policy for COVID-19 in the United States," said Lauren Gardner, co-director of the Center for Systems Science and Engineering at Johns Hopkins, who led the research team.

"Critically, if individual-level actions were not taken and social distancing behavior was delayed until the state-level directives were implemented, COVID-19 would have been able to circulate unmitigated for additional weeks in some locations, inevitably resulting in more infections and deaths," Gardner added. "This demonstrates that it is within the power of each U.S. resident to help slow the spread of COVID-19."

Despite some county-level restrictions being implemented earlier than state policies, 21 out of the 25 counties recorded initial declines in movement before even those local steps.

Determining the effectiveness of social distancing is difficult because counties and states implemented different policies at different times. To establish a reliable indicator of social distancing the researchers used real-world mobile phone movement data.

Their first step was to establish a baseline of normal movement between Jan. 8-31. They then examined changes through April 16 in the 25 U.S. counties with the highest numbers of confirmed COVID-19 cases.

From Jan. 24 to April 17, people made far fewer daily trips than they did during the baseline period. Individuals began to reduce movement in early March, indicating that social distancing began well before the first state, California, imposed a stay-at-home directive on March 21.

In New York City, for example, residents had limited movement to 35% of the baseline, the most-significant reduction in movement among the 25 jurisdictions.

Harris County, Texas, which includes Houston, displayed the least change. Its residents slowed their normal movements but only to 65% of the movements measured in January. Data for all 25 counties are detailed in the research.

Social distancing will remain one of the most important ways to control the spread of infections until a vaccine is available.

"Individuals seem to have anticipated public health directives in March and April, despite a mixed political message," Hamada Badr, a co-author and research scientist in the Department of Earth and Planetary Sciences at Johns Hopkins. "As stay-at-home policies began to relax, we urge individuals and governments to make safe and data-driven decisions, to respond to the potential risk of increased infections. More timely, consistent and decisive policy implementation of social distancing and other known effective mitigation measures is urgently needed."

https://www.sciencedaily.com/releases/2020/07/200702100547.htm

Barriers to addiction care fell because of COVID-19; Now the challenge is keeping them down

July 1, 2020

Science Daily/Michigan Medicine - University of Michigan

The opioid and addiction epidemic didn't go away when the coronavirus pandemic began. But rapid changes in regulations and guidance made during COVID-19 response could also help many more people get care for opioid use disorder and other addiction problems.

That's according to experts from the University of Michigan Addiction Center and VA Ann Arbor Healthcare System, writing in this week's issue of JAMA Psychiatry.

They document the recent policy changes that have made it possible for more addiction care to take place through telemedicine, specifically video chats and even telephone calls. They also note the requirements for in-person visits for key addiction treatments that have been waived -- though only temporarily -- during COVID-19.

Yet despite the recent rapid progress, they say, it will take more changes to truly lower barriers that stand in the way of delivering evidence-based addiction care to more people via telemedicine.

If that happens, more people with substance use disorders could have access to care such as medications, psychotherapy and peer group support, they say -- even in rural areas and other places where addiction specialists are scarce.

Some of the authors already used telehealth as part of their work at the VA even before the COVID-19 pandemic began. Based on that experience, and on the intense shifts to virtual care in the past three months, they give specific recommendations for how to make telehealth for addiction a sustainable option for more providers and patients.

"Before COVID, treatment of substance use disorders was one of the least-used forms of telemedicine, because of a combination of regulatory issues, clinician comfort and patient comfort," says Allison Lewei Lin, M.D., M.Sc., the lead author and an addiction psychiatrist at the U-M and VA.

"Now, many addiction providers haven't seen their patients in the office, or have substantially decreased in-person visits, by using telemedicine in the past three months," she says. "And where we once relied on referring patients to inpatient and residential programs, many of those have not been available during this time, so outpatient clinicians have been trying to take care of sicker patients as well."

Policy shifts

Relaxation of rules such as the Ryan Haight Act, which previously didn't allow prescribers to prescribe buprenorphine and other controlled addiction treatment medications to patients they had only seen virtually, have made a big difference, says Lin.

So have changes in rules and guidance from the Substance Abuse and Mental Health Services Administration to make it easier for clinicians to communicate and care for patients with addiction via telemedicine.

Plus, the same changes to Medicare and Medicaid telemedicine reimbursement rules that have helped move non-addiction care online this spring are helping addiction providers, too.

More research needed

As the coronavirus pandemic continues, she says, many in the addiction field have a lot of questions -- ones that researchers are now scrambling to study. For instance, how are patients doing, and are they improving with telemedicine-delivered treatment? Also of intense interest: Can telemedicine potentially help patients start and stay engaged in treatment longer than they would have with traditional care?

The rapid move to virtual care has been a big switch for a field that has focused for so long on building interpersonal rapport between patient and provider -- and also on in-person checks such as urine tests to make sure patients are adhering to their treatment and spot relapses early.

"Patients are now used to telemedicine and some really like it, so we shouldn't take it away even when coronavirus wanes," Lin says. "But we have to evaluate the impacts, including if the treatments are actually effective, as we go on."

Last year, Lin led a team that published a review of the existing evidence surrounding telemedicine for substance use disorders. They concluded that much more research was needed -- but that early evidence showed efficacy and high patient satisfaction.

Key recommendations

In the new piece, she and colleagues Anne Fernandez, Ph.D., M.A. and Erin Bonar, Ph.D. recommend three key changes going forward:

• Development of treatment guidelines that include both in-person and telemedicine-based care for substance use disorders, and that provide guidance on urine toxicology practices and use of new ways to monitor treatment progress including self-monitoring apps and other practices.

• More work to increase the availability of buprenorphine via telemedicine, including by increasing the number of physicians who are trained to prescribe it and monitor patients taking it. This could especially help rural areas hit hard by the opioid epidemic. Lin and her colleagues currently lead regular training sessions to get new providers started with such prescribing, and offer ongoing support for prescribers.

• More help for people with substance use disorders who are also coping with other mental health conditions, and with the psychological and financial stress brought on by the COVID-19 pandemic. Online resources including group therapy online will be key, they say.

"In this moment when clinical care has been transformed because of real-world necessity, rather than evidence produced by research, it makes research on the effects of that transformation all the more urgent," says Lin. "We need to understand to what extent we should be offering telemedicine even after COVID-19 has subsided."

Another urgent issue: making sure that patients in rural areas without broadband Internet access aren't left behind.

Lin has been seeing addiction patients for years using telehealth, but they had to travel to a clinic in a nearby city in order to connect with her. Now she is having visits with those patients in their homes instead.

"These past few months have been a natural experiment for substance use disorder treatment, much of which has traditionally been largely outside the realm of other types of medicine," she says. "It will be important to see how things change, for better or worse. When we have the option for in-person care again, we will also need to determine which is better -- telemedicine or the traditional approach -- and for which patients to keep them engaged and make care more accessible, especially for vulnerable populations."

Lin, Bonar and Fernandez are all faculty in the U-M Department of Psychiatry, part of Michigan Medicine, as well as members of the U-M Institute for Healthcare Policy and Innovation and the U-M Injury Prevention Center.

https://www.sciencedaily.com/releases/2020/07/200701125434.htm

COVID-19 causes 'hyperactivity' in blood-clotting cells

June 30, 2020

Science Daily/University of Utah Health

Changes in blood platelets triggered by COVID-19 could contribute to the onset of heart attacks, strokes, and other serious complications in some patients who have the disease, according to University of Utah Health scientists. The researchers found that inflammatory proteins produced during infection significantly alter the function of platelets, making them "hyperactive" and more prone to form dangerous and potentially deadly blood clots.

They say better understanding the underlying causes of these changes could possibly lead to treatments that prevent them from happening in COVID-19 patients. Their report appears in Blood, an American Society of Hematology journal.

"Our finding adds an important piece to the jigsaw puzzle that we call COVID-19," says Robert A. Campbell, Ph.D., senior author of the study and an assistant professor in the Department of Internal Medicine. "We found that inflammation and systemic changes, due to the infection, are influencing how platelets function, leading them to aggregate faster, which could explain why we are seeing increased numbers of blood clots in COVID patients."

Emerging evidence suggests COVID-19 is associated with an increased risk of blood clotting, which can lead to cardiovascular problems and organ failure in some patients, particularly among those with underlying medical problems such as diabetes, obesity, or high blood pressure.

To find out what might be going on, the researchers studied 41 COVID-19 patients hospitalized at University of Utah Hospital in Salt Lake City. Seventeen of these patients were in the ICU, including nine who were on ventilators. They compared blood from these patients with samples taken from healthy individuals who were matched for age and sex.

Using differential gene analysis, the researchers found that SARS-CoV-2, the virus that causes COVID-19, appears to trigger genetic changes in platelets. In laboratory studies, they studied platelet aggregation, an important component of blood clot formation, and observed COVID-19 platelets aggregated more readily. They also noted that these changes significantly altered how platelets interacted with the immune system, likely contributing to inflammation of the respiratory tract that may, in turn, result in more severe lung injury.

Surprisingly, Campbell and his colleagues didn't detect evidence of the virus in the vast majority of platelets, suggesting that it could be promoting the genetic changes within these cells indirectly.

One possible mechanism is inflammation, according to Bhanu Kanth Manne, Ph.D., one of the study's lead authors and a research associate with the University of Utah Molecular Medicine Program (U2M2). In theory, inflammation caused by COVID-19 could affect megakaryocytes, the cells that produce platelets. As a result, critical genetic alterations are passed down from megakaryocytes to the platelets, which, in turn, make them hyperactive.

In test tube studies, the researchers found that pre-treating platelets from SARS-CoV-2 infected patients with aspirin did prevent this hyperactivity. These findings suggest aspirin may improve outcomes; however, this will need further study in clinical trials. For now, Campbell warns against using aspirin to treat COVID-19 unless recommended by your physician.

In the meantime, the researchers are beginning to look for other possible treatments.

"There are genetic processes that we can target that would prevent platelets from being changed," Campbell says. "If we can figure out how COVID-19 is interacting with megakaryocytes or platelets, then we might be able to block that interaction and reduce someone's risk of developing a blood clot."

This study titled, "Platelet Gene Expression and Function in COVID-19 Patients," was funded by the National Institutes of Health, the University of Utah Health 3i Initiative, and the American Heart Foundation.

https://www.sciencedaily.com/releases/2020/06/200630125129.htm