Urgent need for coronavirus testing in care homes, suggests study

by Kate Wighton, Imperial College London

Credit: CC0 Public Domain

A team of academics from the UK Dementia Research Institute (UK DRI) has undertaken a coronavirus outbreak investigation in four London nursing homes.

22 Jun 2020--The research, which has not yet been peer-reviewed, showed 26 percent of residents across four nursing homes died between March and May, three times the rate in previous years.

High rates of coronavirus infection (40 percent) were detected, and 60 percent of those infected were asymptomatic or had atypical symptoms.

Specific, tailored measures are needed to manage coronavirus infection in care homes, say the research team, including comprehensive and repeated testing

The researchers worked with GPs, infectious diseases experts, a geriatric clinical outreach team and Local Authority colleagues to undertake a coronavirus outbreak investigation in four London nursing homes. The multidisciplinary team was convened by Hammersmith & Fulham Council's Director of Public Health, after large numbers of residents at one of the homes became unwell at the end of March.

Using a robotic testing platform developed by the UK DRI team earlier in the month, 313 residents and a selection of staff were tested for the virus to assess infection rates and identify the particular challenges facing nursing homes in controlling an outbreak. A report from the investigation, authored by UK DRI researchers and published as a preprint on MedRxiv, found that comprehensive and repeated testing of both residents and staff are vital to controlling infection rates in nursing homes.

Four-hundred-sixteen-thousand people in the UK live in care homes, where COVID-19 has led to very high levels of illness and death. The World Health Organisation has estimated that as many as half of all COVID-19 deaths in Europe are in care homes. However, little information is available to understand the details of outbreaks in the care home context.

Many people infected without showing symptoms

The team, which included academics from the UK DRI's Care Research and Technology centre based at Imperial College London and the University of Surrey, tested the residents at two time points a week apart, with systematic testing starting on 15 April. Clinical and demographic information was also collected and studied.

A sample of asymptomatic nursing home staff in a variety of roles were also tested to clarify the role that unrecognised staff infections may play in viral transmission. Test results were reported back to residents and care staff promptly to inform decisions on how to minimise further infection.

All of the nursing homes involved had experienced an outbreak of COVID-19, and together saw 103 deaths across a total population of 394 residents between 1 March and 1 May. This was three times the death rate in previous years. Around half of the deaths were attributed to COVID-19 on the death certificate, and over half of those who died had dementia.

Care homes suffered significant outbreaks

Testing found that 40 percent of residents were positive for coronavirus, with 60 percent of these being asymptomatic or displaying only atypical symptoms. Four percent of the asymptomatic staff sample tested positive, suggesting that staff are likely to be a factor in transmitting infection. Viral sequencing showed multiple distinct clusters of SARS-CoV-2 in the same nursing homes.

The study found that COVID-19 often presented in an atypical way—if at all—in nursing home residents: respiratory symptoms such as a cough or shortness of breath often existed already in patients and hallmark signs such as fever were often absent. Many residents, particularly those with the highest care needs, displayed no symptoms at all in the lead up to death. This means that usual approaches to infection control that rely on the identification of symptoms, contact tracing and isolation, are ineffective.

Professor David Sharp, joint senior author of the investigation and Director of the UK DRI's Care Research and Technology Centre based at Imperial College London and the University of Surrey, said:

"We know that many nursing homes have suffered significant outbreaks but until now there's been little data on prevalence, infection rates and what's needed in this setting to combat the virus. The number of deaths in the four homes we studied shows just how pressing an issue this is.

"Dealing with an outbreak of this nature in a nursing home presents many challenges. We found that a very high proportion of those testing positive had no symptoms, or different symptoms from those expected. This makes it extremely difficult for staff to recognise illness and take appropriate measures to protect those they care for. Universal and systematic testing of residents and staff is needed across nursing homes if infection is to be contained.

"The logistics of mass testing are challenging and nursing homes will likely need increased resource to be able to do it well. We were fortunate to be working with a fantastic team of GPs, infectious diseases experts, a geriatric clinical outreach team and colleagues from the Council. This was a prime example of people from different fields and settings coming together and acting quickly as a team to help tackle the virus to protect the most vulnerable."

Testing vital to understanding the virus

Professor Bart de Strooper, Director of the UK Dementia Research Institute, said:"This investigation demonstrates how systematic testing is vital to our understanding of the virus, how it is transmitted, and how it can be contained. By recognising that many people in nursing homes are becoming unwell, often with no symptoms, infection control measures can be adapted, having an immediate impact.

"The UK DRI exists to transform the lives of people with dementia, so when we saw an opportunity to deliver a rapid project to benefit vulnerable older people, we mobilised resource and technology to make sure we could get results fast.

"Our team had already created a new high-throughput coronavirus testing platform in just nine days last month and the speed of this project has been no less staggering. A little over a week after the first conversation with colleagues about introducing testing in nursing homes, every resident had been tested in four homes."

Dr. Nicola Lang, Acting Director of Public Health and Consultant in Public Health Medicine for Hammersmith & Fulham Council, said:"In response to the care home outbreaks, we rapidly drew together what now feels like a unique collaboration between GPs, virology, elderly medicine, frailty matrons, infectious diseases teams, academia, and paediatric infectious diseases and epidemiology teams.

"They helped me manage the outbreaks with the latest advice, enabling us to test all our residents twice, and also start care home staff testing.

"This rapid testing informed the actions we took with nursing home colleagues, and strengthened our infection control and isolation procedures.

"The legacy is a mature partnership which has already created guidance for many types of COVID-19 situations with elderly patients."

Alarming findings

Fiona Carragher, Director of Research and Influencing for Alzheimer's Society, which part-funded the study through its support of the UK DRI, said:

"This is just a snapshot of the devastation that coronavirus is wreaking in care homes. While a small study, it is alarming that there were three times more deaths than usual, with over half of these being people with dementia. Additionally, over 60 percent of residents who tested positive were asymptomatic, or didn't display the symptoms we're associating with COVID-19.

"At least seven in ten people in care homes have dementia, and it's clear that to keep them safe, we need regular, systematic testing of all residents and staff regardless of symptoms.'

"Our funded researchers have done excellent work to understand the reality of COVID-19 and dementia on the frontline, laying the groundwork for more extensive studies to build on, so we can develop a truly evidenced based approach to keeping people with dementia and all care home residents safe during the pandemic."

Dr. Carol Routledge, Director of Research at Alzheimer's Research UK, which part-funded the study through its support of the UK DRI, said:

"We urgently need to understand the way that COVID-19 is spreading in care homes so we can better protect residents, staff, and their families.

"With over two thirds of people in care homes living with dementia, it's great to see dementia researchers joining efforts to understand the COVID-19 outbreak in these facilities. Recent studies suggest that people with dementia are at higher risk of severe COVID-19 symptoms, and this is an additional source of worry for them and their families.

"The government must be doing all it can to limit infections and prevent further COVID-19 deaths in care homes.

"While this study has collected important data relevant to an ongoing health crisis, the findings have not yet been reviewed by outside experts. This peer review, an important step in medical research, will also be vital for helping to inform government policy."

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More information: Neil SN Graham et al. SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes, (2020). DOI: 10.1101/2020.05.19.20105460

Provided by Imperial College London 

Nursing homes represent more than 1 in 4 COVID-19 deaths

by Justin Myers and Ricardo Alonso-Zaldivar

In this April 20, 2020, file photo, emergency medical technicians transport a patient from a nursing home to an emergency room bed at St. Joseph's Hospital in Yonkers, N.Y. Nursing home residents account for nearly 1 in 10 of all the coronavirus cases in the United States and more than a quarter of the deaths, according to an Associated Press analysis of government data released Thursday, June 18. (AP Photo/John Minchillo, File)

Nursing home residents account for nearly 1 in 10 of all the coronavirus cases in the United States and more than a quarter of the deaths, according to an Associated Press analysis of government data released Thursday.

21 Jun 2020--As federal data collection becomes more robust, a clearer picture is emerging of the ravages of COVID-19 in nursing homes. About 1.4 million older and medically frail people live in such facilities, a tiny share of the American population that has borne a crushing burden from the pandemic. Most residents have been in lockdown since early March, isolated from families and friends, even in death.

AP's analysis of data from the Centers for Medicare and Medicaid Services found that nearly half of the more than 15,000 nursing homes have reported suspected or confirmed cases of COVID-19 as of June 7. About 1 in 5 facilities—or 21%—have reported deaths.

Nationwide, nursing homes reported nearly 179,000 suspected or confirmed cases among residents and 29,497 deaths. The latest figures include about 95% of nursing homes.

Earlier this week, a special House panel on the coronavirus pandemic launched an investigation into the crisis in nursing homes.

The vulnerabilities are many. Residents live in close quarters, usually two to a room before the pandemic. They shared dining and recreational areas, and physical therapy gyms. Many staff aides work in several facilities, so they can unwittingly carry the virus from one nursing home to another.

Lawmakers are concerned "that lax oversight by the Centers for Medicare and Medicaid Services and the federal government's failure to provide testing supplies and personal protective equipment to nursing homes and long-term care facilities may have contributed to the spread of the coronavirus," said committee Chairman James Clyburn, D-S.C. "Despite CMS's broad legal authority, the agency has largely deferred to states, local governments, and for-profit nursing homes to respond to the coronavirus crisis."

But CMS chief Seema Verma has said that "trying to finger-point and blame the federal government is absolutely ridiculous." She says nursing homes with poor ratings on infection control are more likely to have high numbers of cases, a claim that academic researchers say they have not been able to substantiate.

Republican lawmakers also have blamed some Democratic governors who issued orders requiring nursing homes to take recovering coronavirus patients. New York rescinded its directive after Gov. Andrew Cuomo faced an outcry.

The AP's analysis also found that:

— Among states, New Jersey had the highest proportion of nursing homes with suspected or confirmed COVID-19 cases, about 82%. This comprises 299 of the state's 363 nursing homes.

— Massachusetts had the highest proportion of nursing homes with COVID deaths, nearly 66%. That represented 247 of the state's 376 nursing homes.

— In 30 states, nursing homes' share of COVID-19 deaths was higher than the national average of 26.7%. In some of the hardest-hit, such as Connecticut and Massachusetts, more than one-third of the state's deaths occurred in nursing homes.

The AP has previously reported a higher number of 45,500 deaths, but that count incorporates assisted living facilities, not just nursing homes, and includes staff. The federal data reported Thursday is for nursing homes, since CMS does not regulate assisted living facilities.

Consumers will have access to coronavirus information through Medicare's many states have yet to meet a White House goal to test every resident and staff member for COVID-19. That was supposed to have happened before the end of May.

Also unmet is a separate federal goal for state inspectors to assess all nursing homes for infection control. There is no deadline, but federal officials are growing impatient. As of a couple of weeks ago, only a few states had inspected all facilities.

Even before the coronavirus pandemic, many nursing homes had "persistent" problems with infection control, according to a recent report from the Government Accountability Office, a watchdog agency for Congress.

Thorough, methodical, ongoing testing of residents and staff is considered one of the keys to making nursing homes safer.

Federal officials have recommended a one-time test for all residents and staff, as well as weekly retesting of staff. Nursing homes should retest residents weekly until none test positive.

Verma says states should use "extreme caution" before reopening nursing homes to visitors.

Keeping COVID-19 from nursing home residents requires money and improved infection control

by Kathryn Hyer, David Dosa and Lindsay J. Peterson, The Conversation

Credit: CC0 Public Domain

At least 11 people have died from COVID-19 in New Orleans nursing homes in the past week, just after the deaths at a Seattle nursing home weeks ago showed the extreme danger of the virus in nursing home settings.

21 Jun 2020--Nursing homes provide care for 1.3 million Americans every day in the U.S. Under normal circumstances, these residents are more vulnerable to illness because they frequently are of advanced age and have multiple chronic conditions, such as diabetes and heart disease. COVID-19 now presents a new and dangerous threat.

Residents of the Life Care Center in Kirkland, Washington, near Seattle, were among the first in the U.S. to die from COVID-19. The frightening speed with which the virus has emerged in other long-term facilities raises urgent questions: How can nursing homes protect their residents? Should they admit patients with the virus? And what should they do if a resident becomes infected? These questions require immediate answers.

As a research team, we study quality of care in long-term care. That includes disaster planning for nursing homes. Based on recent decisions made by our government, we are not certain all is being done to stop the spread of the virus within these facilities.

CDC regulations aren't stringent enough

More than two weeks ago, the Centers for Medicare and Medicaid Services imposed strict limitations on nursing home visits, albeit with some exceptions for end-of-life situations. While these measures are undoubtedly protecting nursing home residents across the country, they have not been universally effective, as we see from the cases now erupting.

Extreme vigilance to these limitations is essential, meaning that families and friends must accept the precautions and find alternatives to communicating with those they care about, not only in nursing homes but assisted living communities and all other senior care homes. Also, every possible step must be taken to ensure that nursing home staff are not carrying the virus.

That said, there are alarming gaps in the government's plan for protecting nursing homes. There are no requirements that nursing homes keep known or suspected COVID-19 residents in isolation rooms. Instead, the Centers for Disease Control and Prevention recommends only that they be placed in private rooms, preferably with their own bathrooms. What's more, facilities are advised they can accept new residents diagnosed with the virus as long as they follow the prescribed CDC precautions.

These guidelines ignore the extreme risk the disease poses to other nursing home residents and staff. They also ignore the lapses, evident in many nursing homes, in adequate infection control.

A 'clear and present danger'

Medical professionals working in long-term care are alarmed, particularly over the prospect that nursing homes will be forced to accept COVID-19 patients. A March 19 resolution from the Society for Post-Acute and Long-Term Care Medicine says the infection poses a "clear and present danger" to nursing home residents. The resolution also highlights a lack of preparedness at nursing homes to handle the "severity and complexity" of managing COVID-19 patients.

The resolution urges local, state and federal governments to establish specialized care sites for COVID-19 patients, away from nursing home residents to whom contact with the virus may well be deadly. Others have made similar recommendations.

Viral outbreaks are not new to nursing homes. Exposure to influenza and gastrointestinal illnesses such as norovirus causes a multitude of infections in these facilities every year. Regulations already require nursing homes to create and maintain their own prevention and control programs for communicable diseases. Despite that, a recent University of South Florida analysis of federal nursing home records found some disturbing statistics: Nearly 60% of nursing homes were cited at least once for inadequate infection control between 2017-19; 15% were cited multiple times. Equally disturbing is that new regulations were to include requirements for a full-time staffer in every facility with specialized training to manage the infection control program. However, this past November the Centers for Medicare and Medicaid Services delayed the regulatory training required to implement the rule.

Enabling nursing homes to operate effectively during a pandemic requires a clear-eyed understanding of their capabilities, and limitations. They are obligated to follow regulatory requirements, yet limited by reimbursement rates. While nursing homes routinely accept previously hospitalized patients for convalescence and rehab as part of their role in the health care system, the novel coronavirus presents an unprecedented challenge: The homes don't have the equipment or staff to care for a COVID-19 level of infection.

To prevent more deaths in nursing homes, the nursing home industry must begin to aggressively advocate for their patients through increased reimbursement and resource allocation. Bottom line: These facilities urgently need more equipment, including effective facial protection and gowns and staff with the necessary infectious disease training. Alternate sites, away from uninfected patients, must be established to care for patients being treated for and recovering from COVID-19. Dedicated staffing should be established for all COVID-19 patients to minimize transmission of the virus within the facility through staff. Additional Medicare reimbursement for nursing home patients with COVID-19 would also help to defray some of the costs borne by nursing home facilities during this outbreak.

In the meantime, all of us need to remember this: Even places with the best infection control program will have difficulty caring for COVID-19 patients. Nursing homes provide skilled care for a specific, highly impaired segment of the population—but they are not hospitals. They are not designed or equipped to provide the hospital level of containment and care that COVID-19 patients require. While the Monday morning quarterbacking that will most certainly occur downstream will be imperative to prepare nursing homes for future outbreaks of COVID-19 or other such pathogens, the findings should not become fodder for punitive action against staff or management who are simply trying to do the best they can under dire circumstances.

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Provided by The Conversation

Study ties blood type to COVID-19 risk; O may help, A hurt

by Marilynn Marchione

In this June 12, 2020, file photo, a health worker draws blood for COVID-19 antibody testing in Dearborn, Mich. A genetic analysis of COVID-19 patients published Wednesday, June 17, 2020, in the New England Journal of Medicine suggests a person's blood type may have some influence on whether they develop severe disease. (AP Photo/Paul Sancya, File)

A genetic analysis of COVID-19 patients suggests that blood type might influence whether someone develops severe disease.

19 Jun 2020--Scientists who compared the genes of thousands of patients in Europe found that those who had Type A blood were more likely to have severe disease while those with Type O were less likely.

Wednesday's report in the New England Journal of Medicine does not prove a blood type connection, but it does confirm a previous report from China of such a link.

"Most of us discounted it because it was a very crude study," Dr. Parameswaran Hari, a blood specialist at the Medical College of Wisconsin, said of the report from China. With the new work, "now I believe it," he said. "It could be very important."

Other scientists urged caution.

The evidence of a role for blood type is "tentative ... it isn't enough of a signal to be sure," said Dr. Eric Topol, head of the Scripps Research Translational Institute in San Diego.

The study, involving scientists in Italy, Spain, Denmark, Germany and other countries, compared about 2,000 patients with severe COVID-19 to several thousand other people who were healthy or who had only mild or no symptoms. Researchers tied variations in six genes to the likelihood of severe disease, including some that could have a role in how vulnerable people are to the virus. They also tied blood groups to possible risk.

Most genetic studies like this are much larger, so it would be important to see if other scientists can look at other groups of patients to see if they find the same links, Topol said.

Many researchers have been hunting for clues as to why some people infected with the coronavirus get very ill and others, less so. Being older or male seems to increase risk, and scientists have been looking at genes as another possible "host factor" that influences disease severity.

There are four main blood types—A, B, AB and O—and "it's determined by proteins on the surface of your red blood cells," said Dr. Mary Horowitz, scientific chief at the Center for International Blood and Marrow Transplant Research.

People with Type O are better able to recognize certain proteins as foreign, and that may extend to proteins on virus surfaces, Hari explained.

During the SARS outbreak, which was caused by a genetic cousin of the coronavirus causing the current pandemic, "it was noted that people with O blood type were less likely to get severe disease," he said.

Blood type also has been tied to susceptibility to some other infectious diseases, including cholera, recurrent urinary tract infections from E. coli, and a bug called H. pylori that can cause ulcers and stomach cancer, said Dr. David Valle, director of the Institute of Genetic Medicine at Johns Hopkins University.

Bottom line: "It's a provocative study. It's in my view well worth publishing and getting out there," but it needs verification in more patients, Valle said.

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More information: David Ellinghaus et al. Genomewide Association Study of Severe Covid-19 with Respiratory Failure, New England Journal of Medicine (2020). DOI: 10.1056/NEJMoa2020283

Journal information: New England Journal of Medicine 

Study sheds light on a classic visual illusion

by Anne Trafton, Massachusetts Institute of Technology

An MIT-led research team has discovered evidence that a classic visual illusion called simultaneous brightness contrast, such as the one seen here, relies on brightness estimation that takes place in the retina, not the brain’s visual cortex. In this image, the two small discs appear to have different brightness despite having identical luminance. Credit: Massachusetts Institute of Technology

It's a classic visual illusion: Two gray dots appear on a background that consists of a gradient from light gray to black. Although the two dots are identical, they appear very different based on where they are placed against the background.

17 Jun 2020--Scientists who study the brain have been trying to figure out the mechanism behind this illusion, known as simultaneous brightness contrast, for more than 100 years. An MIT-led study now suggests that this phenomenon relies on brightness estimation that takes place before visual information reaches the brain's visual cortex, possibly within the retina.

"All of our experiments point to the conclusion that this is a low-level phenomenon," says Pawan Sinha, a professor of vision and computational neuroscience in MIT's Department of Brain and Cognitive Sciences. "The results help answer the question of what is the mechanism that underlies this very fundamental process of brightness estimation, which is a building block of many other kinds of visual analyses."

As one part of their investigation, the researchers studied blind children in India and found that they were susceptible to this illusion almost immediately after their sight was initiated after surgery, offering further evidence that brightness estimations are likely based on simple neural circuitry that doesn't require any prior visual experience to be set up.

Sinha is the senior author of the study, which appears in the August issue of Vision Research. Other authors of the paper are Sarah Crucilla, who worked with Sinha while she was in high school and is now a Caltech undergraduate; Tapan Gandhi, a faculty member at the Indian Institute of Technology and a former postdoc at MIT; Dylan Rose, a recent Northeastern University Ph.D. recipient; Amy Singh of Google, who is also a former MIT postdoc; Suma Ganesh and Umang Mathur of Dr. Shroff's Charity Eye Hospital in New Delhi; and Peter Bex, a professor of psychology at Northeastern University.

Estimating brightness

When we look at an image, our brain perceives a certain brightness at each location of the image. Surprisingly, however, our brightness percepts are not always proportional to the amount of light emanating from image regions, Sinha says. Instead, our perception is the product of the object's actual color and the amount of light that is shining on it.

"You could have a really dark piece of cloth under a bright spotlight, and the amount of light that you get from it could be the same as, or even more than, the amount of light from a white piece of paper under dim light," Sinha says. "The brain is presented with the challenge of figuring out how light or dark a surface is based on just the amount of energy it's receiving. In essence, the brain has to figure out the two numbers that were multiplied (illumination level and surface darkness) to produce the one number it is receiving (incoming energy)—a seemingly impossible task since infinitely many pairs of numbers can all yield the same product."

Some scientists, including the 19th century German physicist Hermann von Helmholtz, an early pioneer of vision studies, suggested that estimating brightness is a "high-level" process. That is, the brain estimates brightness based on a high-level understanding of the lighting conditions, shapes, and shadows in the environment that it's seeing.

Many visual tasks, such as identifying faces or objects, do rely on our previous experiences or expectations about what we're seeing. However, the experiments that Sinha and his colleagues performed in this study suggest that in the case of brightness estimation, high-level processing does not play a significant role.

In this second example of simultaneous brightness contrast, two cuboids stacked one on top of the other look fairly similar, but they have different effects on identical dots placed on their faces. The upper cuboid makes the right dot look brighter, while the lower one makes the left dot appear brighter. Credit: Massachusetts Institute of Technology

In their first set of experiments, the researchers created an image of a cube that appeared to be lit from the side, with one face appearing a little brighter than the other. In reality, using a clever trick that Chinese ceramic painters knew over 800 years ago, the face that looked brighter actually had lower luminance than the face that looked darker. In this display, the researchers found that when identical gray dots were placed on the two cube faces, the dot that was on the face that seemed to be in shadow actually appeared darker than an identical dot placed on a face that was receiving more light.

"This is the opposite of what happens in standard simultaneous contrast displays, in which a dot on a dark background appears brighter than a dot on a light background," Sinha says. "This result runs counter to the idea that high-level analysis of lighting conditions contributes to brightness estimation."

The second set of experiments was designed to localize the processes of brightness estimation. It built on the curious fact that the unified view of the world we experience, constructed by merging images from the two eyes, is accompanied by an almost complete loss of "eye of origin" information. We do not know what the original images were, and which eye they came from; we are only aware of the merged view (sometimes called the "cyclopean" image, after the one-eyed monster Cyclops of Greek mythology). However, using specially designed images and stereo glasses, the researchers found that brightness estimation did not need to wait until information from the two eyes was merged; it had already occurred by that point.

This finding suggests that brightness estimation occurs very early, before information coming from each eye is combined into one visual stream. The combination occurs in a part of the brain's cortex called V1 (so named because it represents the first stage of visual processing in the cortex). This places a tight constraint on the location of processing; the researchers hypothesize that significant brightness computation most likely takes place in the retina.

"The implication of results from the first two sets of studies was that if brightness estimation is really a low-level process, and the circuitry is located as early as the retina, then perhaps this is an innate dispensation," Sinha says. "This is something that the visual system comes prepared to do, right from birth."

"An innate mechanism"

The researchers were able to explore this hypothesis by studying blind children who had recently had their sight restored. Sinha runs an effort in India called Project Prakash, whose mission is to treat children suffering from preventable forms of blindness such as congenital cataracts. Many of the treated children go on to participate in scientific studies of visual development, although treatment is not contingent on such participation.

"The prediction was that if brightness estimation is truly an innate mechanism, then right after sight is initiated in children who were congenitally blind, they should fall prey to the simultaneous contrast illusion," Sinha says.

That is exactly what the researchers found, in a study of nine children who had cataracts surgically removed between the ages of 8 and 17. All of the children were susceptible to the illusion, in tests done just 24 to 48 hours after their surgical bandages were removed.

In a 2015 study, Sinha showed that recently sighted children are also immediately susceptible to two other visual illusions, known as the Müller-Lyer and Ponzo illusions, which involve judging the length of lines based on visual cues.

"The account that emerged from that work also seems to be consistent with the account that's emerging from the brightness studies. That is, many of the phenomena that we are so quick to ascribe to high level inferential processes may actually be instantiated in some very simple circuit mechanisms of the brain that are innately available," Sinha says. "These results are contributing to the quest for understanding how our nervous systems solve the complex challenge of perceiving and understanding the world around us."

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More information: Pawan Sinha et al. Mechanisms underlying simultaneous brightness contrast: Early and innate, Vision Research (2020). DOI: 10.1016/j.visres.2020.04.012

Provided by Massachusetts Institute of Technology 

Cheap drug is first shown to improve COVID-19 survival

by Marilynn Marchione

Packages of Dexamethasone are displayed in a pharmacy, Tuesday, June 16, 2020, in Omaha, Neb. Researchers in England said Tuesday they have the first evidence that the drug can improve COVID-19 survival. The cheap, widely available steroid called dexamethasone reduced deaths by up to one third in severely ill hospitalized patients. (AP Photo/Nati Harnik)

Researchers in England say they have the first evidence that a drug can improve COVID-19 survival: A cheap, widely available steroid reduced deaths by up to one third in severely ill hospitalized patients.

16 jun 2020--The results were announced Tuesday and the British government immediately authorized the drug's use across the United Kingdom for coronavirus patients like those who did well in the study. Researchers said they would publish results soon in a medical journal, and several independent experts said it's important to see details to know how much of a difference the drug, dexamethasone, might make and for whom.

But "bottom line is, good news," said the United States' top infectious disease expert, Dr. Anthony Fauci. "This is a significant improvement in the available therapeutic options that we have."

The coronavirus outbreak has killed more than 438,000 people worldwide since it began late last year in China.

The study, led by the University of Oxford, was a large, strict test that randomly assigned 2,104 patients to get the drug and compared them with 4,321 patients getting only usual care.

The drug was given either orally or through an IV for 10 days. After four weeks, it had reduced deaths by 35% in patients who needed treatment with breathing machines and by 20% in those only needing supplemental oxygen. It did not appear to help less ill patients.

Researchers estimated that the drug would prevent one death for every eight patients treated while on breathing machines and one for every 25 patients on extra oxygen alone.

"Those are big effects," said one study leader, Dr. Martin Landray at Oxford. "It's not a cure, but it's certainly a long way forward." It's especially good news that the drug "is remarkably cheap, perhaps $20 or $30 for an entire course of treatment," he added.

Steroid drugs reduce inflammation, which sometimes develops in COVID-19 patients as the immune system overreacts to fight the infection. This overreaction damages the lungs and can prove fatal. The World Health Organization and others advise against using steroids earlier in the course of illness because they can impede clearing the virus.

"Early on, you're fighting the virus and you want your immune system to be as intact as possible," Fauci explained. But in the advanced stage of COVID-19, the battle against the virus causes so much inflammation that it "is hurting you more than helping you," he said. The results seen in the Oxford study make "perfect sense" with that notion, he said.

Many hospitals and doctors have been trying steroids to quell the immune system, but there's been no evidence from high-quality studies that it helps for COVID-19.

Although the Oxford researchers talked only about dexamethasone, the detailed plans for the study say that participating hospitals could use two other steroids—prednisolone or hydrocortisone—and there's no reason to think any particular one works better than another, said Dr. Francisco Marty, an infectious disease specialist at Brigham and Women's Hospital in Boston.

"I assume the majority of people used dexamethasone, but it's not the only one that people could have used," he said. "It will be great to see the data to see if there's a class effect."

In this Sunday, June 14, 2020 file photo, medical workers attend to a COVID-19 patient in an intensive care unit at a hospital in Sanaa, Yemen. Researchers in England say they have the first evidence that a drug can improve survival from COVID-19. The drug is a cheap, widely available steroid called dexamethasone. Results released Tuesday, June 16 show it reduced deaths by up to one third in severely ill hospitalized patients. (AP Photo/Hani Mohammed, File)

Steroids are known to help fight certain fungal and bacterial infections such as meningitis, and a type of pneumonia common in HIV patients, but they have not proved useful against flu or some other viral diseases, he said. The Oxford results would persuade him to try them for COVID-19 patients needing extra oxygen, he said.

Until now, the only drug shown to help fight COVID-19 is remdesivir, an experimental drug from Gilead Sciences that blocks an enzyme the virus uses to copy its genetic material. Remdesivir shortened the time to recovery for severely ill hospitalized patients to 11 days on average versus 15 days for those just given usual care, in a study led by the U.S. National Institutes of Health.

"We don't know yet" if remdesivir could be used with dexamethasone—or before or after it—to give more benefit, Fauci said.

Even though dexamethasone only helps in severe cases, "countless lives will be saved globally," said Nick Cammack, a virus expert at the Wellcome Trust, a British charity that supports research.

"This is the dream," because the drug has been used for decades for other conditions, said Cammack, who had no role in the study. "It's very straightforward to make so there's no reason this can't be rolled out for the entire world."

No information was given on side effects, but researchers said they used a low dose and for a short time, which is generally safe.

"Short-term low dose shouldn't be a problem, but steroids do have a lot of side effects" including weight gain, high blood pressure, water retention, mood changes, sleep problems and rise in blood sugar for people with diabetes, Marty said.

Dr. Peter Bach, a health policy expert at Memorial Sloan-Kettering Cancer Center in New York, noted that in the study 41% of those on breathing machines and 25% on oxygen alone died.

"The mortality rate seems to be way higher than it is in the U.S.," where one recent study found a death rate of 12%, although that was only after two weeks versus four in the UK study, he said.

"We are going to struggle to look at these data and use them for U.S. patients," he said. But he added that "it's good news for science that the right studies got done," and that the drug works and is so affordable and available.

The Oxford study is the same one that earlier this month showed the malaria drug hydroxychloroquine was not working against the coronavirus. The study enrolled more than 11,000 patients in England, Scotland, Wales and Northern Ireland who were given either standard care or that plus one of several treatments: dexamethasone; hydroxychloroquine; the HIV combo drug lopinavir-ritonavir; the antibiotic azithromycin; the anti-inflammatory drug tocilizumab; or plasma from people who have recovered from COVID-19 that contains antibodies to fight the virus.

Research is continuing on the other treatments. The research is funded by government health agencies in the United Kingdom and private donors including the Bill and Melinda Gates Foundation.

Dr. Stephen Griffin, of the University of Leeds in England, said treatments that can prevent infection and serious illness are still needed.

"Ideally, we will find something that stops the disease from progressing to a more advanced stage," he said, noting that remdesivir might yet prove to be effective this way. Dexamethasone "is not a wonder pill, but it will lessen some of the nasty effects of COVID-19."

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The Associated Press. 

Up to 45 percent of SARS-CoV-2 infections may be asymptomatic

by The Scripps Research Institute

Credit: CC0 Public Domain

An extraordinary percentage of people infected by the virus behind the ongoing deadly COVID-19 pandemic never show symptoms of the disease, according to the results of a Scripps Research analysis of public datasets on asymptomatic infections.

13 jun 2020--The findings, published in Annals of Internal Medicine, suggest that asymptomatic infections may account for as much as 45 percent of all COVID-19 cases, playing a significant role in the early and ongoing spread of COVID-19. The report highlights the need for expansive testing and contact tracing to mitigate the pandemic.

"The silent spread of the virus makes it all the more challenging to control," says Eric Topol, MD, founder and director of the Scripps Research Translational Institute and professor of Molecular Medicine at Scripps Research. "Our review really highlights the importance of testing. It's clear that with such a high asymptomatic rate, we need to cast a very wide net, otherwise the virus will continue to evade us."

Together with behavioral scientist Daniel Oran, Topol collected information from testing studies on 16 diverse cohorts from around the world. These datasets—gathered via keyword searches of PubMed, bioRxiv and medRxiv, as well as Google searches of relevant news reports—included data on nursing home residents, cruise ship passengers, prison inmates and various other groups.

"What virtually all of them had in common was that a very large proportion of infected individuals had no symptoms," says Oran. "Among more than 3,000 prison inmates in four states who tested positive for the coronavirus, the figure was astronomical: 96 percent asymptomatic."

The review further suggests that asymptomatic individuals are able to transmit the virus for an extended period of time, perhaps longer than 14 days. The viral loads are very similar in people with or without symptoms, but it remains unclear whether their infectiousness is of the same magnitude. To resolve that issue, we'll need large-scale studies that include sufficient numbers of asymptomatic people.

The authors also conclude that the absence of symptoms may not imply an absence of harm. CT scans conducted on 54 percent of 76 asymptomatic individuals on the Diamond Princess cruise ship, appear to show significant subclinical lung abnormalities raising the possibility of SARS-CoV-2 infection impacting lung function that might not be immediately apparent. The scientists say further research is needed to confirm the potential significance of this finding.

The authors also acknowledge that the lack of longitudinal data makes distinguishing between asymptomatic and presymptomatic individuals difficult. An asymptomatic individual is someone who is infected with SARS-CoV-2, but never develops symptoms of COVID-19, while a presymptomatic person is similarly infected, but will eventually develop symptoms. Longitudinal testing, which refers to repeated testing of individuals over time, would help differentiate between the two.

"Our estimate of 40 to 45 percent asymptomatic means that, if you're unlucky enough to get infected, the probability is almost a flip of a coin on whether you're going to have symptoms. So to protect others, we think that wearing a mask makes a lot of sense," Oran concludes.

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More information: Daniel P. Oran et al, Prevalence of Asymptomatic SARS-CoV-2 Infection, Annals of Internal Medicine (2020). DOI: 10.7326/M20-3012

Journal information: Annals of Internal Medicine 

New app analyzes how social distancing affects biological clocks

by Morgan Sherburne, University of Michigan

Screenshots of the Social Rhythms iOS app. Credit: Social Rhythms

Almost overnight, the sleep and wake patterns of nearly four billion people may have changed because of COVID-19-spurred lockdowns.

11 jun 2020--A free app built by University of Michigan researchers will help users understand their own sleep rhythms, shedding light on how their biological clock is responding to lockdowns, and give tips about how to shift their potentially disrupted rhythms to a more appropriate time.

The data generated by the app could also give scientists an unprecedented opportunity to examine disruption in circadian rhythms. Circadian rhythms are internal clocks in our cells that regulate when we sleep, when we wake, when we eat and even our digestion. If these clocks are disrupted, a cascade of ill effects may occur, including a weakened immune system.

The new Social Rhythms iOS app assesses how a person's circadian rhythm changed before and after the COVID-19 pandemic. The app allows users to understand how their own body clocks have been impacted and provide researchers with anonymized data to study the impact of disrupted circadian rhythms on a person's health.

"During social distancing, lockdown or quarantine, many of the key signals which tell our body what time it is, such as access to outdoor light, are blocked. Additionally, many signals which confuse our internal clocks, such as light from screens, have skyrocketed," said Daniel Forger, U-M professor of mathematics.

"Some adults may also have their circadian timekeeping disrupted while caring for other individuals—young children—whose biological clocks run very differently."

Others may benefit from the crisis, such as individuals who no longer have to work night shifts.

"In short, many of us may be experiencing circadian disruption which could lead to fatigue, mood changes, changes in sleep patterns and decreased immune function," said Forger, also a professor of computational medicine and bioinformatics and faculty affiliate at the Michigan Institute for Data Science at U-M.

The app analyzes an individual's circadian rhythms before and after social distancing. Users answer simple demographic questions, then upload data from their phones, Apple Watches, MiBands or FitBits.

Algorithms on the group's servers analyze the data, which then is used to generate a report for the user. The report uses straightforward graphics to show the user whether his or her biological timekeeping has shifted earlier or later. It also can point to other potential concerns about circadian timekeeping, such as whether the individual's rhythms are becoming more irregular or if there is a disconnect between timekeeping between different parts of the body.

"What also is very unhealthy is some people are going to bed at 2 a.m. one day and then 8 p.m. the next day and midnight the next day," Forger said. "You'll be notified if your rhythm becomes more irregular or if it shifts later."

The app will help the U-M researchers build a vast database of information about circadian rhythms. The data will be stripped of identifying information, but will allow the researchers to study how this kind of disruption impacts a person's health and compare an individual's health as a consequence of circadian rhythm shifts. Participants can delete their data at any time.

Forger and his group, in collaboration with Chris Stockbridge of the U-M College of Literature, Science, and the Arts Information Technology, were originally developing this app to study major life events such as having a baby or beginning work on a night shift. But then, the coronavirus crisis happened.

"It presented the biggest global change in circadian rhythms of our lifetime," Forger said.

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More information: Social Rhythms iOS app: apps.apple.com/us/app/social-rhythms/id1510826025

Provided by University of Michigan 

The fascinating history of clinical trials

by Adrian Esterman, The Conversation

Credit: CC0 Public Domain

Clinical trials are under way around the world, including in Australia, testing COVID-19 vaccines and treatments.

06 jun 2020--These clinical trials largely fall into two groups. With observational studies, researchers follow a group of people to see what happens to them. With experimental studies, people are assigned to treatments, then followed.

These study designs have come about from centuries of people trying out different ways of treating people.

Here are some of the key moments in the history of clinical trials that led to the type of trials we see today for COVID-19.

Ginseng in 11th-century China

One of the earliest observational studies occurred nearly 1,000 years ago in China. The 1061 Atlas of Materia Medica (Ben Cao Tu Jing) was compiled and edited by Song Su, a renowned scientist, administrator, diplomat and military strategist.

It documented a trial of ginseng: "[…] to evaluate the effect of genuine Shangdang ginseng, two persons were asked to run together. One was given the ginseng while the other ran without. After running for approximately three to five li [about 1,500-2,500 metres], the one without the ginseng developed severe shortness of breath, while the one who took the ginseng breathed evenly and smoothly."This observational study is also the first recorded example of a control group.

A control group can be patients who are not treated at all, patients who receive a standard treatment compared to a new one, or patients who receive a placebo (a treatment or substance designed to have no therapeutic effect).

Having a control group is one of the cornerstones of modern clinical trials.

An example of a control group in COVID-19 research is this recent study. People with diabetes hospitalised for COVID-19 were divided into those receiving the drug metformin and those not receiving it (the control group).

Back to ginseng. Today, it is a popular herbal remedy. As to whether it improves stamina, a recent review found some evidence ginseng might help men with erectile dysfunction.

Rhubarb in 18th-century England

Rhubarb roots have been used as a laxative for more than 5,000 years, including in 18th-century England.

Caleb Parry, an English physician working in Bath, wanted to know whether locally grown rhubarb was as good as the more expensive Turkish variety.

In 1786, he ran a study in which he switched the type of rhubarb he gave to each patient at different times. He then compared each patient's symptoms while eating each type of rhubarb. He concluded there was no advantage in using the Turkish version.

This is the first published example of a crossover trial (a study where the participants receive each treatment at different times).

Today, we know rhubarb roots and stems are rich in anthraquinones, which have a laxative effect.

Early 20th-century randomised trial

Beriberi, a disease that can have lasting effects on the nervous system and heart, was common in Southeast Asia in the early part of the 20th century.

In 1905 a beriberi outbreak occured at the Kuala Lumpur Lunatic Asylum. At that time William Fletcher was the district surgeon. He realised the outbreak provided an excellent opportunity to run an experiment (which we now know is just a bit unethical).

Each patient was assigned a number. Those with even numbers were sent to one ward and given brown unpolished rice to eat. Those with odd numbers went to another ward and given white polished rice.

At the end of the experiment, 15% of the patients who ate the white rice died of beriberi; none given brown rice died.

This is a very early example of randomisation in a clinical trial, where one group is chosen at random to receive a treatment.

Randomisation is another very important factor in good clinical trial design.

Today we know beriberi is caused by a deficiency in thiamine (vitamin B1) and a white rice diet is deficient in thiamine.

Tuberculosis and the randomised controlled trial

Sir Austin Bradford Hill, an English epidemiologist and statistician, conducted the first randomised controlled trial in 1948. The trial was to treat the lung disease tuberculosis.

Bradford Hill decided whether a patient should be treated with the antibiotic streptomycin plus bed rest, or bed rest alone, by using a table of random numbers.

The investigators didn't know which patient got each treatment; details were in sealed envelopes. Patients were not told they were in a trial.

Using sealed envelopes is an example of what we now call allocation concealment. Making sure neither investigators nor patients know which treatment they are receiving is called blinding. These are now standard features of randomised controlled trials.

Randomised controlled trials are the "gold standard" of clinical trial designs, due to the use of both a control group and randomisation.

Decades later, researchers have used a randomised controlled trial to test the drug ruxolitinib in patients with severe COVID-19.

So, although Bradford Hill conducted the first randomised controlled trial, it was based on hundreds of years of people working out why things like a control group and randomisation are so important.

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Provided by The Conversation