Low-cost ventilatory support for COVID-19 patients

by University of Leeds

Credit: University of Leeds

A research team at Leeds has developed a way of creating a ventilatory system for COVID-19 patients that can be made rapidly on a 3-D printer.

26 april 2020--It is a low-tech solution based on redesigning an existing medical device known as a Venturi valve. It does not need electricity and has no moving parts and could be made in countries without access to advanced manufacturing facilities.

Known as the Leeds Venturi valve, the remodelled device is subject to regulatory approval.

This is the second time in a month that the research team has found a way of repurposing existing medical technology to increase the number of breathing aids available for patients.

In this latest development, the researchers from the University of Leeds, Leeds Teaching Hospitals NHS Trust (LTHT) and Bradford Teaching Hospitals NHS Foundation Trust, focused on the Venturi valve—a small plastic device normally used to increase the flow of oxygen to a patient.

One end of the valve is attached to the oxygen-supply pipe by a patient's bed or to an oxygen cylinder. The other end connects to the tubing that goes to the person's oxygen mask.

The repurposed device not only delivers an increased flow of oxygen to the patient, it also raises the pressure of that flow, opening the tiny air sacs in the lungs that are damaged by the virus and allowing oxygen to get into the body.

Importantly, the device produces an effect similar to a continuous positive airway pressure, or CPAP, machine—a form of intermediate-level ventilator capable of delivering oxygen at the right concentration and pressure to have a therapeutic effect.

Medical reports from China have indicated that moderately ill people can be treated on CPAP machines and avoid the need for full mechanical ventilation, which is often only available in hospital intensive care units and required for the sickest patients.

Dr. Tom Lawton, Consultant in Critical Care and Anaesthesia at Bradford Teaching Hospitals, who collaborated on the project, said: "We are already seeing that treating COVID-19 patients with CPAP can help avoid the need for ventilators and intensive care; the key is to do this in a resource-efficient way.

The valves being manufactured in a 3D printing machine at the University of Leeds. Credit: University of Leeds

"Devices like this venturi valve could be a key to expanding the use of CPAP across the globe."

Maxillofacial Surgeon Jiten Parmar, from Leeds Teaching Hospitals NHS Trust, another member of the research team, said: "This collaborative work has allowed for the innovation of a therapeutic oxygen delivery device for use in countries where there may be a lack of CPAP machines or oxygen supply."

Two weeks ago, the researchers announced details of how a device used to help people with a condition called sleep apnoea could be adapted to treat COVID-19 patients. There are thought to be thousands of machines across the NHS that could be used this way.

Dr. Pete Culmer, Associate Professor in the School of Mechanical Engineering at the University of Leeds, said: "Our work has focused on investigating more rapid ways of getting life-saving technology to the side of patients as the pandemic spreads.

"Across the world, there have been concerns about increasing the number of ventilators that are available. We have now looked at two solutions. Both involve adapting existing technologies and that dramatically reduces the time it takes to get equipment to the patient's bedside.

"Taking established technology and repurposing it means there is a greater chance that we can make real our solutions in a timely and effective way."

The researchers have put their findings online.

Nikil Kapur, Professor of Applied Fluid Mechanics in the School of Mechanical Engineering, leads the research team. He said: "We set out to make sure that the Leeds Venturi valve had two significant improvements over existing Venturi valves.

"One, that they made efficient use of hospital oxygen supplies—vital given that the demand on supplies is likely to be high—and two, that they could be easily manufactured.

"As the pandemic sweeps across the world, researchers need to think about solutions and technologies that can be implemented in developing countries. This is one of those solutions."

Venturi valves are not new devices and are based on observations made by Italian physicist Giovanni Venturi in the late 1700s.

More information: Peter Culmer et al. Delivery of CPAP respiratory support for COVID-19 using repurposed technologies, (2020). DOI: 10.1101/2020.04.06.20055665

Provided by University of Leeds 

5 ways the COVID crisis has created an ageism crisis—and what to do about it

by Manfred Diehl, Colorado State University

Credit: CC0 Public Domain

Researchers who are studying the human aging process from a behavioral perspective are getting increasingly concerned that their efforts to reduce ageism in our society are being rapidly undone during the COVID-19 crisis. Ageism includes the propagation of negative age stereotypes, discrimination against older adults, and stigmatization based on age.

26 april 2020--Here are five ways in which the COVID-19 crisis has also created an ageism crisis that requires everyone's attention.

1. In public discussions, older adults are regularly referred to as "the elderly." The use of this word is viewed as derogatory in nature by many professional organizations, including the Gerontological Society of America and the American Psychological Association. The reason for that is that the word "elderly" invokes images of frailty, vulnerability and senility. Yet, the overwhelming majority of older adults (e.g., persons over the age of 60 or 65) are neither frail, vulnerable or senile. Indeed, the majority of older adults lead vigorous and productive lives.
2. The public discussions also ignore that a person's age is, in general, not a good indicator of that person's level of functioning, and that older adults are the most diverse age group in our society. Therefore, a person's age should not become the sole criterion for whether this person receives testing or treatment during the COVID-19 crisis. Other criteria, such as a person's symptoms, preexisting health conditions, and other risk factors should become the decisive factors—for both older and younger adults. Indeed, it is important to not withhold important health care from younger adults (e.g., reversed ageism) with the argument that they are reserved for older adults. Such an approach only sows intergenerational division where intergenerational solidarity is needed.
3. Although the public emphasis on older adults' greater susceptibility to COVID-19 may be well-intentioned, it is also important to keep in mind that it is not age per se that makes older adults more susceptible. Rather, it is the co-morbidities that are more likely to happen as individuals get older that make a person more vulnerable. For example, a 50-year-old with asthma, type 2 diabetes, and cardiovascular disease may be more vulnerable to the COVID-19 virus than a healthy 70-year-old. Again, age alone is just a number and we should not stigmatize anybody because of that number.
4. Another aspect of ageism that has reoccurred in public debates is the "greedy old geezer" argument. That is, older adults may create a disproportional burden on societal resources, such as the health-care system, that would be better invested in younger generations. Although it is correct that the rate of hospitalizations and fatalities is higher for older adults, currently it is not clear at all whether this is also the case for the rate of infections. As the pandemic unfolds, it may well be that the rate of infections will actually turn out to be significantly higher in younger age groups. This is another reason why it is important to refrain from blaming the old and to engage in intergenerational solidarity. Let's face it: We are all in this together!
5. Finally, it is important to acknowledge that many older adults are making valuable contributions to their communities during the COVID-19 pandemic. Increasingly we are hearing stories that retired nurses and doctors are responding to the needs of their local communities and help provide services in testing lines, emergency rooms, and on hospital floors. Other activities that older adults are contributing to in their communities is helping with the production of protective gear, helping with child care, and serving as caregivers to loved ones. Again, it is important to acknowledge these valuable contributions and to refrain from thinking that "old = worthless."

In summary, behavioral aging researchers advocate for a balanced portrayal of older adults in our society and remind us that later adulthood is a life stage that we all—if we have the good fortune to live long enough—will experience at some point in time.

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Provided by Colorado State University 

ST-segment elevation described in patients with COVID-19

For patients with COVID-19 who have ST-segment elevation, indicating potential acute myocardial infarction, there is considerable variability in presentation, and prognosis is poor, according to a letter to the editor published online April 17 in the New England Journal of Medicine.

24 april 2020--Sripal Bangalore, M.D., from New York University Grossman School of Medicine in New York City, and colleagues describe their experience involving patients with confirmed COVID-19 who had ST-segment elevation on electrocardiography from six New York hospitals.

The researchers identified 18 patients with ST-segment elevation indicating potential acute myocardial infarction (median age, 63 years; 83 percent male), of whom 33 percent had chest pain around the time of ST-segment elevation. Ten patients had ST-segment elevation at the time of presentation and eight developed ST-segment elevation during hospitalization. Five of 14 patients with focal ST-segment elevation had a normal left ventricular ejection fraction, one of whom had a regional wall-motion abnormality. Eight patients had a reduced left ventricular ejection fraction. Nine patients underwent coronary angiography and six of these had obstructive disease; five patients underwent percutaneous coronary intervention. Higher median peak troponin and D-dimer levels were seen among the eight patients who received a clinical diagnosis of myocardial infarction versus the 10 with noncoronary myocardial injury. Thirteen patients died in the hospital, including four and nine with myocardial infarction and noncoronary myocardial injury, respectively.

"In this series of patients with COVID-19 who had ST-segment elevation, there was variability in presentation, a high prevalence of nonobstructive disease, and a poor prognosis," the authors write.

More information: Abstract/Full Text

Some COVID-19 patients stricken by Guillain-Barre syndrome

by E.j. Mundell, Healthday Reporter

Studies are beginning to show that, in rare cases, people with severe COVID-19 may develop the serious nervous system disorder known as Guillain-Barre syndrome.

23 april 2020--"Guillain-Barre syndrome is a well-known condition in which one's immune system targets peripheral nerves as foreign and attacks them, resulting in the cardinal features of the disease," explained Dr. Anthony Geraci, who directs neuromuscular medicine at Northwell Health in Great Neck, N.Y.

The symptoms of the disorder "include weakness, areflexia [absence of reflexes], paresthesia [tingling], and in some cases facial weakness and ataxia [poor balance]," Geraci said.

It's not uncommon for severe cases of infectious disease to trigger Guillain-Barre, experts noted. According to the Italian authors of a new study, the syndrome has also been seen in patients battling Epstein-Barr virus, cytomegalovirus and, most notably, infection with mosquito-borne Zika.

The new study was authored by a team of doctors battling a major outbreak of COVID-19 in the northern Italian city of Pavia.

Reporting in the April 17 online edition of the New England Journal of Medicine, the authors said that between Feb. 28 and March 21, three hospitals in the region treated about 1,200 patients with COVID-19. Five of those patients displayed symptoms most likely caused by Guillain-Barre, the team said.

Symptoms of Guillain-Barre tended to arise within five to 10 days of the first onset of common COVID-19 symptoms, the researchers said. These first Guillain-Barre symptoms included weakness in the legs, tingling and facial weakness. Within another two days, neurologic symptoms got worse until all four limbs were weakened or paralyzed, the Italian group said.

All five patients received immune globulin therapy to boost their immune response to the coronavirus, and one patient was treated with the antibody-rich blood plasma of a COVID-19 survivor.

A month into treatment, "two patients remained in the intensive care unit [ICU] and were receiving mechanical ventilation, two were undergoing physical therapy because of flaccid paraplegia and had minimal upper-limb movement, and one had been discharged and was able to walk independently," according to the report.

Dr. Sami Saba is a neurologist at Lenox Hill Hospital in New York City. Reading over the findings, he agreed that "many infections can be triggers for Guillain-Barre syndrome, so it is not entirely surprising that we are seeing cases associated with the novel coronavirus."

Saba stressed that because many ICU patients with COVID-19 are sedated and on mechanical ventilation, it's tough to even tell if their limbs are functioning as they should.

"In those cases, weakness and sensory loss can be very difficult to identify if they are not awake, moving their limbs, or able to tell you what they are experiencing," Saba said. "However, since Guillain-Barre can affect the muscles that help us breathe, it will be very important to consider the diagnosis in those who have trouble coming off the ventilator, especially if their lung function looks to be recovering."

For his part, Geraci stressed that Guillain-Barre remains quite rare—just five cases out of 1,200 in this new study. He agreed that a variety of tests are needed before a firm diagnosis of the syndrome can be made.

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More information: Head to the U.S. National Institute of Neurological Disorders and Stroke for more on Guillain-Barre syndrome.

Journal information: New England Journal of Medicine 

A study looks at how to disinfect your mask at home

by Roland Yan, Steve Chillrud, Debra Magadini, and Beizhan Yan, Columbia University

A new study suggests that disposable surgical masks can be disinfected with heat multiple times without harming their effectiveness. A homemade plastic nose clip, used here, may add another layer of protection. Credit: Beizhan Yan

Due to the unknown numbers of asymptomatic people infected with the SARS-CoV-2, the Centers for Disease Control and Prevention has recommended that all citizens wear face coverings when in public. More recently, some states have mandated face coverings. Many people are wearing homemade coverings, but these mandates potentially increase demand for medical face masks, exacerbating shortages for first responders and medical staff.

22 april 2020--One way to to extend the supply of disposable masks is to disinfect them and reuse them. We have just published a paper in the Journal of the International Society for Respiratory Protection that looks into whether disposable masks can be disinfected by heating them without compromising their effectiveness. We also compared the effectiveness of medical-grade masks with homemade ones, and looked into the feasibility of improving masks with homemade nose clips.

Prior work by others on disinfection of disposable masks has shown that heating for 30 minutes at 158 degrees F (70 C) or above can effectively destroy SARS, influenza and the novel SARS-CoV-2 coronavirus. This can be done in a home oven. As such, we did no testing with viruses. Instead we focused on whether repeated heat disinfection affected how well the masks worked for removing particles in the same size range as coronavirus.

To do this, we put masks onto mannequin heads, and rigged the heads to "breathe" through their noses and mouths, using a vacuum pump. We then exposed the mannequins to black carbon (i.e, soot) from a kerosene lamp, which generates particles that overlap in size with those of the coronavirus. We determined filtration efficiency by comparing black-carbon levels on both sides of the masks worn by the mannequins. We did this with two brands of disposable N95 respirators and one brand of disposable surgical mask, as well as with one design of homemade face covering. We tried this out repeatedly, and in a variety of ways.

One of three homemade face coverings tested out by the researchers. The silicone headform was a donation from Joshua Turi. Credit: Beizhan Yan

First, to measure the maximum filtration efficiency and resilience of the disposable masks, each disposable mask type was tested while taped or modified to tightly fit a plastic mannequin's face when new, and again after each heating cycle. We found that one N95 brand (3M) and a surgical mask (HSl brand) stood up to the 10 cycles of heat disinfection and reuse, with no reduction in performance. Filtration efficiency was greater than 95 percent over all 10 cycles for N95 respirators, and greater than 70 percent for surgical masks. (In contrast, we found that the nose-pad of another N95 brand, the Moldex, was unable to withstand multiple cycles of being put on and off the mannequin, whether or not it was heated in between uses.)

These tests show the maximum filtration efficiency possible, but they are not representative of how people normally wear masks, where the fit can be much looser. So, for a second set of tests, we obtained a head form covered in soft silicone to mimic the pliability of the human face. We then assessed the effectiveness of the masks as they are commonly worn, by simply putting the elastic straps around the head or ears without additional tightening. As expected, the filtration efficiency of all the disposable masks decreased substantially, to around 40 percent. This confirms that the effectiveness of such masks relies upon a tight fit, and this may be hard for many people to achieve.

We also tested the filtration efficiency of three homemade cloth coverings made following instructions on the CDC website. We made one from a cotton dress, one from a cotton sweater, and the third from polyester cloth. All three were worn in a normal mode on the silicone head form as directed by the CDC. The filtration efficiency of the cotton homemade cloth coverings in normal use was 55 percent, while the polyester covering came in at near 40 percent—about the same as loosely fitted medical-grade masks. This suggests that homemade cotton masks might actually work better than loosely fitted disposable masks, while polyester might be about the same.

We heated up the homemade masks for disinfection, which appeared to not affect the filtration efficiency. The CDC recommends washing and drying such coverings at home and we anticipate negligible effects on efficiency from this as well. When disinfecting your masks at home, we recommend you to place masks in an oven bag or a pressure cooker during heating, rather than directly put masks inside of the oven (see the instruction video below for details).

Credit: Columbia University

Finally, to see if we could improve the fit for the public, we designed a process that uses heat-moldable plastic strips to make homemade customized nose clips molded to an individual's face. By adding the customized nose clip to a normally worn disposable mask on a silicone head form, the filtration efficiency of the 3M N95 returned to greater than 95 percent, and the filtration efficiency of the surgical masks was measured at 88 percent. The nose clips passed two five-hour wearing tests for comfort. But due to the use of heat moldable plastic, the customized nose clips cannot be disinfected with heat; rather, they must be disinfected by soaking in solutions of alcohol or bleach.

This work has certain limitations. For one, our tests were all done under static conditions at a constant flow rate of air similar to how an adult breathes when sitting. We did not take into account the increase in breathing, nor the reduction in fit that can occur when someone is talking or active.

Our study is just one of many looking into how masks may be disinfected and reused. Others have been carried out or are in progress using not only heat, but ultraviolet light, vaporized hydrogen peroxide, or soaking in ethyl alcohol or bleach solutions. Most of these are aimed at medical personnel using specialized equipment. The soaking methods have been shown to reduce the effectiveness of certain types of N95 masks. Ours is a relatively modest effort aimed at everyday usage. Far more work needs to be done, but everything we know so far suggests that wearing almost any kind of mask in public is better than nothing; that a tight fit is best; and that, with certain limits, many types of masks can be reused outside of medical settings.

More information: Developing home-disinfection and filtration efficiency improvement methods for N95 respirators and surgical facial masks: stretching supplies and better protection during the ongoing COVID-19 pandemic. Journal of the International Society for Respiratory Protection. https://www.isrp.com/the-isrp- … 20-pp-19-35-yan/file

Provided by Columbia University 

There is no evidence that the coronavirus was created in a laboratory

by Eric Muraille, The Conversation

Credit: CDC / Unsplash, CC BY

The COVID-19 pandemic, which is disrupting our lives and shaking our health systems and economies, is at the root of what Dr. Sylvie Briand, director of the Department of Pandemic and Epidemic Diseases of the World Health Organization (WHO), rightly described as an infodemic – the viral circulation of rumours and false information.

21 april 2020--The COVID-19 infodemic

Journalists and so-called experts have seriously suggested that the SARS-CoV-2 coronavirus at the heart of the epidemic could have been produced in the Level 4 Biosafety Laboratory (BL4) in China's Wuhan region, the epicentre of the epidemic.

These theories have gone viral, to the point that recent polls show that 23% of Americans and 17% French believe that the new coronavirus was made intentionally in a laboratory.

The wave of conspiracy theories surrounding the COVID-19 epidemic has also been spurred on by a few governments waging a veritable information war by politicizing the epidemic. In a speech on March 11, 2020, US president Donald Trump called COVID-19 the "Chinese virus". In response, a spokesperson for the Chinese Ministry of Foreign Affairs posted on his Twitter account an article allegedly demonstrating that SARS-CoV-2 was already present in 2019 in the United States and was brought to China by American soldiers.

The spread of such false information can hamper the response to real epidemics, and it is therefore crucial to establish the verifiable facts about SARS-CoV-2 virus.

What do we know about the origins of COVID-19?

The results of the genomic analysis of SARS-CoV-2 are clear: its sequence is 96% identical to that of the RaTG13 coronavirus isolated from a bat collected in the Chinese province of Yunan. The sequence of the receptor binding domain (RBD) present on the surface of SARS-CoV-2 that allows it to infect human cells, however, diverges strongly from the equivalent sequence observed in RaTG13. On the other hand, the RBD sequence of SARS-CoV-2 is very close (99%) to that of a coronavirus isolated in the pangolin. This suggests that SARS-CoV-2 is the result of the recombination of two viruses. This recombination mechanism has already been observed in coronaviruses.

Comparison of coronavirus sequences present in nature supports a natural origin for SARS-CoV-2. Furthermore, SARS-CoV-2 contains no trace of any human-mediated genetic manipulation. More specifically, it does not contain residual sequences related to vector systems conventionally used for genetic manipulation, which suggests that it is indeed the product of natural random selection.

BL4 laboratory, genetic manipulation: reality and myths

There is indeed a BL4 laboratory in Wuhan: the Wuhan National Biosafety Laboratory. Built in partnership with France, it obtained certification in 2017. Following the SARS epidemics of 2002-2004 and H1N1 in 2009, China wanted to improve its capacity to fight epidemics. The laboratory primarily carries out research on Ebola, Crimean-Congo hemorrhagic fever and SARS. The only documented accident linked to a laboratory working on coronaviruses in China was the infection of nine individuals … the SARS-CoV-1 virus responsible for the SARS epidemic of 2002-2004. The people infected were two students working at the National Institute of Virology Laboratory and their relatives.

There are almost 30 BL4 laboratories listed worldwide. Their operations have always been a source of controversy and suspicion, in particular because some were previously involved in the manufacture of biological weapons. With the signing of the 1972 Convention on the Prohibition … f Biological Weapons, which banned the development, acquisition, stockpiling and use of biological weapons, the purpose of the laboratories changed. They now officially work to fight epidemics and biological weapons. However, it has been shown that certain countries, including the former Soviet Union, continued to fund biological-weapons research programs, such as Biopreparat, despite having signed the convention.

These BL4 laboratories have indeed already been linked to accidents. For example, the 1979 Sverdlovsk disaster, which involved the accidental spread of spores of … m Bacillus anthracis that causes anthrax, caused dozens of deaths. The 2001 anthrax attacks in the United States were linked to a microbiologist, Bruce Ivins, who was working in a US Army BL4 laboratory. These high security laboratories have thus provided fertile ground for the development of highly extravagant conspiracy theories.

It is also true that ancient deadly viruses have been resuscitated in the laboratory, that new viruses are created by genetic manipulation for research purposes, and that some viruses have already been disseminated in the wild by countries. In 2005, the 1918 Spanish influenza virus was genetically engineered and tes … ed in the laboratory to better understand its exceptional virulence. In 2012, the H5N1 flu virus was modified in the laboratory to give it the ability to infect ferrets by air to understand how the virus could mutate to infect humans by the same route. In 2017, the Australian government authorised the spread of a strain of rabbit hemorrhagic disease virus (RHDV1 K5) to reduce the population of wild rabbits on its territory. These well-documented events have also provided good fodder for an infinite variety of scenarios.

Russel's teapot and COVID-19

What do a "celestial teapot" and the conspiracy theories surrounding COVID-19 have in common? More than you might think at first glance.

The metaphor of the celestial teapot was proposed by the philosopher Bertrand Russell to challenge the idea that it is up to the sceptic to refute the unverifiable bases of religion and to affirm that the burden of proof falls instead to the believer. Russell suggested that a teapot is in orbit around the sun, precisely between Earth and the planet Mars. We cannot demonstrate that this teapot does not exist, so we have to believe it is there. Russel's teapot is the cosmic version of Ockham's razor, also known as the principle of parsimony or simplicity. This principle recommends eliminating complex explanations for a phenomenon from reasoning if simpler explanations prove plausible. There remains a fundamental principle of logical reasoning in science: it does not state that the simplest explanation is necessarily true, only that it must be considered first.

In the case of COVID-19, there is no verifiable fact to support the hypothesis that SARS-CoV-2 was intentionally manufactured in a laboratory. Various conspiracy theories are only supported by correlations, such as the existence of a BL4 in Wuhan. The RBD sequences of the virus could, in theory, result from an adaptation of the virus in the laboratory when cultured in human cells. But the existence of an RBD sequence that is 99% identical in a coronavirus infecting the pangolin supports a more parsimonious hypothesis: the infection of a bat or a pangolin with two coronaviruses that recombined to form a new virus that in turn infected a human, who would then be the famous and still unknown patient zero behind the COVID-19 epidemic.

The success of conspiracy theories about COVID-19 reveals much about our visceral need to reassure ourselves by inventing simplistic explanations for terrifying natural phenomena. Which hypothesis is the most unbearable—that mad scientists subsidised by a foreign power sparked an epidemic capable of shaking our modern societies, or that new epidemics emerge because of our invasion and destruction of natural ecosystems? In the first case, it would be easy to end the nightmare. In the second, it is our way of life and our economic system that must change.

Provided by The Conversation 

People with COVID-19 may be infectious days before symptoms: study

by Kelly MacNamara

The study comes amid concern over patients who may be infectious despite not showing signs of ill health

People infected with the new coronavirus may start spreading the virus several days before they have any noticeable symptoms, according to a new modelling study published Wednesday.

20 april 2020--The study comes as nations have broadened restrictions aimed at curbing the epidemic, amid concerns over patients who may be infectious despite not showing signs of ill health.

The findings challenge key assumptions behind measures put in place to stop the spread of the pandemic, such as tracing contacts of an infected person only as far back as the time at which they began to show symptoms.

Experts have long conjectured that some people who do not even know they are infected may transmit the virus.

But the new study suggests that even those who get visibly sick may be highly infectious before the onset of symptoms.

"More inclusive criteria for contact tracing to capture potential transmission events two to three days before symptom onset should be urgently considered for effective control of the outbreak," the authors said in the paper published in Nature Medicine.

Infectious before symptoms show

Researchers compared clinical data on virus shedding from patients at a hospital in China with separate data on "transmission pairs"—where one person is believed to have infected the other—to draw inferences about periods of infectiousness.

The research team co-led by Eric Lau of the University of Hong Kong took throat swabs from 94 patients admitted to Guangzhou Eighth People's Hospital and measured infectiousness from the first day of symptoms for 32 days.

They found that the patients, none of whom were classed as severe or critical, had the highest viral load soon after the onset of symptoms, which then gradually decreased.

The study used publicly-available data on 77 transmission pairs, within China and internationally, to assess how much time elapsed between the onset of symptoms in each patient.

It assumed an incubation period—the time between exposure to infection and appearance of symptoms—of a little over five days.

The authors inferred that infectiousness started 2.3 days before symptoms appeared and was at its peak at 0.7 days before the first signs of illness—although they cautioned that pinpointing the exact timing of the onset of symptoms relied on patient memory.

They estimated that 44 percent of secondary cases in the transmission chains were infected during the pre-symptomatic stage.

Infectiousness was predicted to decrease quickly within seven days.

'Important implications'

Responding to the study, Babak Javid of Tsinghua University School of Medicine in Beijing said the findings would have "important implications" for measures to control the pandemic, such as whether masks should be worn by those with no symptoms.

"This is important because current public health control measures advised, for example, by the WHO and UK government assume that maximum contagion is after symptom onset. Hence one reason masks are not advocated for wearing by asymptomatic members of the public," he said.

Javid added that several studies had now suggested that a large number of patients shed the virus before they show signs of illness and said the findings are "likely to be real and robust".

At the beginning of this month China said it had more than 1,300 asymptomatic coronavirus cases, the first time it has released such data following public concern over people who have tested positive but are not showing symptoms.

As the pandemic has spread, many nations that initially advised only individuals with symptoms to self-isolate and wear masks have expanded their responses to measures that apply across the board.

The US Centers for Disease Control and Prevention (CDC) has said up to a quarter of people who are infected may be asymptomatic.

More information: Temporal dynamics in viral shedding and transmissibility of COVID-19, Nature Medicine (2020). DOI: 10.1038/s41591-020-0869-5 , https://www.nature.com/articles/s41591-020-0869-5

Journal information: Nature Medicine 

Loss of smell and taste validated as COVID-19 symptoms in patients with high recovery rate

by University of California - San Diego

3D print of a spike protein of SARS-CoV-2, the virus that causes COVID-19--in front of a 3D print of a SARS-CoV-2 virus particle. The spike protein (foreground) enables the virus to enter and infect human cells. On the virus model, the virus surface (blue) is covered with spike proteins (red) that enable the virus to enter and infect human cells. Credit: NIH

Loss of smell and taste has been anecdotally linked to COVID-19 infections. In a study published April 12, 2020 in the journal International Forum of Allergy & Rhinology, researchers at UC San Diego Health report the first empirical findings that strongly associate sensory loss with COVID-19, the respiratory disease caused by the novel coronavirus.

20 april 2020--"Based on our study, if you have smell and taste loss, you are more than 10 times more likely to have COVID-19 infection than other causes of infection. The most common first sign of a COVID-19 infection remains fever, but fatigue and loss of smell and taste follow as other very common initial symptoms," said Carol Yan, MD, an otolaryngologist and head and neck surgeon at UC San Diego Health. "We know COVID-19 is an extremely contagious virus. This study supports the need to be aware of smell and taste loss as early signs of COVID-19."

Yan and colleagues surveyed 1,480 patients with flu-like symptoms and concerns regarding potential COVID-19 infection who underwent testing at UC San Diego Health from March 3 through March 29, 2020. Within that total, 102 patients tested positive for the virus and 1,378 tested negative. The study included responses from 59 COVID-19-positive patients and 203 COVID-19-negative patients.

Yan said the study demonstrated the high prevalence and unique presentation of certain sensory impairments in patients positive with COVID-19. Of those who reported loss of smell and taste, the loss was typically profound, not mild. But encouragingly, the rate of recovery of smell and taste was high and occurred usually within two to four weeks of infection.

"Our study not only showed that the high incidence of smell and taste is specific to COVID-19 infection, but we fortunately also found that for the majority of people sensory recovery was generally rapid," said Yan. "Among the Covid-19 patients with smell loss, more than 70 percent had reported improvement of smell at the time of survey and of those who hadn't reported improvement, many had only been diagnosed recently."

Sensory return typically matched the timing of disease recovery. Interestingly, the researchers found that persons who reported experiencing a sore throat more often tested negative for COVID-19.

In an effort to decrease risk of virus transmission, UC San Diego Health now includes loss of smell and taste as a screening requirement for visitors and staff, as well as a marker for testing patients who may be positive for the virus.

Other known symptoms of COVID-19 include fever, fatigue, cough and difficulty breathing. Respondents in Yan's study were most often persons with milder forms of COVID-19 infection who did not require hospitalization or intubation. The findings, she said, underline the importance of identifying early or subtle symptoms of COVID-19 infection in people who may be at risk of transmitting the disease as they recuperate within the community.

"It is our hope that with these findings other institutions will follow suit and not only list smell and taste loss as a symptom of COVID-19, but use it as a screening measure for the virus across the world," Yan said.

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More information: Carol H. Yan et al, Association of chemosensory dysfunction and Covid-19 in patients presenting with influenza-like symptoms, International Forum of Allergy & Rhinology (2020). DOI: 10.1002/alr.22579

Gastrointestinal symptoms common in COVID-19 patients, study reports

by Tracie White, Stanford University Medical Center

Credit: CC0 Public Domain

Fever, cough and shortness of breath are the classic symptoms of COVID-19, but there may be gastrointestinal symptoms, such as nausea and diarrhea, that are getting missed, according to a new Stanford Medicine study.

20 april 2020--Researchers found that, in addition to upper respiratory symptoms, a significant number of those sick with the new virus also suffered from loss of appetite, nausea, vomiting and diarrhea.

The study, one of the earliest on U.S. patients with the coronavirus, was published online April 10 in Gastroenterology. Gastroenterology fellows George Cholankeril, MD, and Alexander Podboy, MD, share lead authorship. Aijaz Ahmed, MD, professor of gastroenterology and hepatology, is the senior author.

"COVID-19 is probably not just respiratory symptoms like a cough," Podboy said. "A third of the patients we studied had gastrointestinal symptoms. It's possible we may be missing a significant portion of patients sick with the coronavirus due to our current testing strategies focusing on respiratory symptoms alone."

Unique situation

As the coronavirus pandemic hit the San Francisco Bay Area in early March, hospitals began canceling elective surgeries and postponing nonemergency patient visits to make room for a surge of coronavirus patients. With their clinics closed and other projects on hold, a group of gastroenterology fellows had time to work together on a project, Podboy said.

"George recognized early on that since Stanford was among the first hospitals to get COVID-19 patients in the U.S., that any type of early experience would be important," he said. "We were in a unique position to look into this subject of gastrointestinal symptoms among coronavirus patients at Stanford."

The researchers were aware of a growing body of research out of China and Singapore that showed a prevalence of GI symptoms in COVID-19 patients, but could find no data on the topic from patients in the United States. They decided to conduct their own study by examining the charts of the earliest group of patients treated for the virus at Stanford Health Care.

Study results

Researchers analyzed data collected from 116 patients who tested positive for the coronavirus at Stanford Health Care from March 4-24. The majority were treated and released from a hospital emergency room or a clinic. A total of 33 were hospitalized, eight of those in an intensive care unit. The median age of the patients was 50, and 53% of them were men. Only one death was reported within the group.

Gastrointestinal symptoms were reported by 31.9% of the patients. The majority of that group described the symptoms as mild. Twenty-two percent said they experienced loss of appetite, 22% had nausea and vomiting, and 12% had diarrhea, the study said.

"We also noticed that 40% of patients had elevated levels of an abnormal liver enzyme, and that those with high levels required more hospitalization," Cholankeril said.

Testing recommended

The researchers suggest that while this data is early and from only a single institution, the results do raise the possibility that people exposed to the coronavirus who are experiencing gastrointestinal symptoms—not just those with respiratory symptoms—should also be tested.

"In our current cohort of patients, all patients had respiratory symptoms prior to the development of gastrointestinal symptoms," Podboy said. "No patients had gastrointestinal symptoms prior to the development of respiratory symptoms or as their only manifestation of COVID-19."

He added, "However, that may be a product of who we were testing. Currently, testing is only offered for patients that meet specific criteria—criteria that often require the presence of pulmonary symptoms."

The researchers plan to study the role of GI symptoms in COVID-19 and their implication on disease severity and hospitalization outcomes, Cholankeril said. They also plan to continue working as a team.

"We had six fellows working together and we were able to go through these charts pretty quickly," Cholankeril said. "It was a terrific collaboration between colleagues to be able to join forces to study this new disease. We think that by looking at patients here at Stanford, it can help improve our understanding of this emerging disease."

More information: George Cholankeril et al. High Prevalence of Concurrent Gastrointestinal Manifestations in Patients with SARS-CoV-2: Early Experience from California, Gastroenterology (2020). DOI: 10.1053/j.gastro.2020.04.008

Journal information: Gastroenterology 

Chest X-ray findings normal for many confirmed COVID-19 cases

Most patients presenting to urgent care centers with confirmed coronavirus disease 2019 (COVID-19) have normal or mildly abnormal findings on chest X-rays (CXRs), according to a study published online April 14 in the Journal of Urgent Care Medicine.

20 april 2020--Michael B. Weinstock, M.D., from the Wexner Medical Center at The Ohio State University in Columbus, and colleagues examined the percentage of normal versus abnormal CXRs in urgent care patients with confirmed COVID-19 and described specific imaging characteristics of abnormal findings on CXR using a database of a large urgent care company in the greater New York City area. A total of 636 CXRs were reviewed among patients with confirmed COVID-19.

The researchers found that although patients were symptomatic enough to warrant imaging, 58.3 percent of the CXRs were normal. Of the 265 abnormal cases, 195, 65, and five demonstrated mild, moderate, and severe disease, respectively. The predominant descriptive findings were interstitial changes and ground glass opacities in 23.7 and 18.9 percent, respectively, of the total number of patients. Locations of the abnormalities were in the lower lobe, bilateral, and multifocal in 33.8, 20.9, and 24.2 percent, respectively. Effusions and lymphadenopathy were infrequently observed.

"In future reports we hope to examine what clinical signs, medical history, and demographic characteristics are associated with normal and abnormal CXR readings in patients with COVID-19," the authors write.

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More information: Abstract/Full Text

A healthy circadian rhythm may keep you sane and increase resilience to fight COVID-19

by Satchin Panda, The Conversation

Social distancing and washing hands have become the frontline in the fight against COVID-19, but there is another powerfully protective resource immediately available to all: your circadian rhythm.

18 april 2020--While isolation and hygiene are effective in reducing the chance of infection, they do little to increase our resilience to the virus so that we suffer less and recover faster. In addition, the stress and worry caused by current trends—school and business closures, self-quarantines and mandates to stay at home—don't help. The strains on our physical and psychological health can leave us even more vulnerable to viruses and other health issues. The answer to boosting your immunity may lie in simple steps you can take to maintain a robust circadian rhythm by developing and following a daily routine.

I head a lab that researches circadian rhythms, the daily cycles of bodily functions that form the foundation of good health. These body clocks, found in nearly every organ of the body and part of the brain, are central and vital to a properly functioning immune system. A synchronized circadian rhythm in the lungs, heart, kidney and brain ensures that the processes in our body go as planned while the immune system can effectively fight and defeat a virus. When the timing systems in the human body are desynchronized, essential organs are compromised, reducing the potency of your immune system. Circadian disruption dampens your immune system and makes a virus harder to defeat.

How do we maintain a robust circadian rhythm?

The answer is as simple as developing a daily routine and sticking to it consistently.

Circadian rhythm in the brain is synchronized to the outside world by light and darkness. Circadian rhythms in the rest of the body are synchronized by when we eat. We can maintain a healthy circadian rhythm by the following simple practices: sleep, eating time, daylight exposure, exercise and stress management.

Sleep is the most profound predictor of a healthy circadian rhythm. When we disturb our sleep, it has effects beyond our brain. Studies have shown that chronically sleep-deprived animals and hum … eaker immune systems, making it easier for even mild infections and viruses to gain entry to the body and cause more damage or even death. Therefore, maintaining a consistent sleep schedule is a powerful strategy to maintain better immunity.

Sleep researchers suggest babies and toddlers may sleep as much as 12 hours each day; children and teenagers should spend nine hours in bed; and adults should try to be in bed for eight hours. Dimming light for two to three hours before bedtime and taking a bath before bed will help you to get a good night's sleep. A bedtime bath also cleanses our body and may wash off any virus that might have stuck to our skin.

When we eat can nurture or torture our rhythms

When we are not asleep, we tend to snack or eat. Studies show that nearly 50% of adults are likely to eat over a 15-hour window or longer. Shift workers who work early morning, evening or overnight sleep and try to catch up with regular life during off-days.

This erratic scheduling may lead t … an even worse eating schedule because of the nature of their work. However, you don't have to be a shift worker to live like one.

Such large eating windows disrupt the body's circadian rhythm and weaken organs, including the gut, liver, muscle, heart, kidney and lungs, making it harder to fight an infection. Conversely, animal and human studies are increasingly showing that eating food and beverages with … 8- to 12-hour window reduces disease and infection risk and improves brain and body health. This style of eating is referred to as time-restricted eating or intermittent fasting.

Light up your mood and dim down before sleep

Finally, light and darkness play a crucial role in the brain's circadian rhythm and brain health. Being outdoors and in daylight for at least 30 minutes each day is a great way to synchronize your brain clock with the outside world. It also reduces depression and anxiety and increases alertness.

In the current climate of hunkering down, staying home and rarely venturing out, not having access to daylight may increase the risk of depressio … other mood disorders. Also of note: The UV portion of sunlight is a disinfectant. Just 30 minutes of UV light on clothing may kill bacteria and viruses that may be attached to the exterior of our clothes.

When it becomes dark outside, reducing exposure to bright indoor light for two to three hours before bed will help you sleep.

An ideal routine

We can incorporate these insights into our daily routine to maintain sleep, eating time, light schedule, exercise and strategies to stay positive to profoundly help millions of people who are now stuck at home or have minimal incentive to go out. My lab has developed a research app, myCircadianClock, to guide people how to monitor and optimize their own circadian rhythms.

A simple plan for adults would include the following:

• Sleep: Aim to spend eight hours in bed each night to allow at least seven hours of sleep. This allows the brain to rest, detoxify and rejuvenate. Teenagers and children older than the age of 10 should try to be in bed for nine to 12 hours each night.
• Diet: Eat within an 8- to 10-hour window of time each day. Note the time you ingest your first calories of the day (beverage or food) and plan on taking your last calories of that day 10 hours later. Make sure that the last calories are consumed two to three hours before bedtime. Such time-restricted eating can be enhanced by being combined with home-cooked healthy food to sustain healthy gut, liver, heart, lung, kidney and immune function. Time-restricted eating may also help shed some extra weight and manage blood pressure, blood glucose and cholesterol.
• Light: Spend at least 30 minutes outdoors during daylight hours to reduce depression, increase alertness and improve mood.
• Stress management: Social distancing can be social isolation, which can lead to increased stress, depression and difficulty in falling asleep. Spend more time with the people you live with and get in touch with your faraway family and friends over video chat. Keep your mind busy with positive thoughts, read some books you wanted to read for a long time, make new music playlists, play some board games or do puzzles. Avoid too much TV and depressing news.
• Exercise: Don't forget to get some exercise. For those of you who feel you are physically less active, try to get in some steps. Walk around the neighborhood, do some simple strength exercise at home. Turn on some music and dance. If you can, get outside for a walk or hike. Try to do your intense exercise in the afternoon when the muscle clock can give you the most benefit of exercise.

The exact time when each family goes to bed, eats, exercises, explores the outdoors or socializes depends on where they live and what other constraints they may have. But it takes only a week to develop and follow such a plan. By the second week, you may begin to see the benefits of healthy circadian rhythms.

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Provided by The Conversation