Posts Tagged ‘coronavirus’


Branyas lives in Olot, a city in Catalonia.

By Jack Guy and Al Goodman

A 113-year-old woman, thought to be the oldest in Spain, has said she feels fine after surviving a brush with coronavirus.

Video footage of Maria Branyas, who was born on March 4 1907, shows the super-centenarian speaking to the director of the care home where she lives in Olot, Catalonia.

“In terms of my health I am fine, with the same minor annoyances that anyone can have,” said Branyas in the video. It was recorded Monday, a spokeswoman for the care home told CNN.

Branyas recovered after a mild case of Covid-19. Her battle started shortly after her family visited her on March 4 to celebrate her 113th birthday, the spokeswoman said.

The family has not been able to visit in person since then. Branyas has lived for 18 years in her own private room at the Santa Maria del Tura nursing home, which is run by the Institute of the Order of San Jose of Gerona, affiliated with the Roman Catholic Church, the spokeswoman said.

Branyas was born in San Francisco in the United States, where her father worked as a journalist, reports the AFP news agency.

Over the course of her long life she has survived two world wars as well as the 1918 flu pandemic, which killed more than 50 million people around the world.

Although Branyas recovered from coronavirus, two residents of the same home died of it. The situation at the care home has since improved, said the spokeswoman.

Spain’s state of emergency, in effect since March 14, has strict confinement measures that remain in place. But with the infection and death rates now declining, the government has lifted some lockdown measures in certain parts of the country, on what it says will be a gradual reopening of activity.

But the initial lifting of these restrictions did not apply to Olot, where Branyas lives.

https://www.cnn.com/2020/05/13/europe/spain-oldest-woman-coronavirus-survivor-scli-intl/index.html


Human cell types within corresponding organs that express the genes for both ACE2 and CTSL (green dot) or both ACE2 and TMPRSS2 (orange dot).

by Chris Baraniuk

When the SARS-CoV-2 virus enters the human body, it breaks into cells with the help of two proteins that it finds there, ACE2 and TMPRSS2. While there has been much discussion of viral infection in gut and lung cells, researchers have dug into massive gene expression datasets to show that other potential target cells also producing ACE2 and TMPRSS2 are scattered throughout the body—including in the heart, bladder, pancreas, kidney, and nose. There are even some in the eye and brain.

The results, published in a preprint on bioRxiv April 21, show that such cells are strikingly abundant. Many are epithelial cells, which line the outer surface of organs. The new findings add to an emerging picture of SARS-CoV-2 as a virus that can target cells in many places in the human body, rather than being focused on a particular organ or part of the respiratory tract.

Cardiologist Frank Ruschitzka at the University Hospital of Zürich and colleagues separately published a letter in The Lancet April 17 in which they described how virus particles had been found in the vascular endothelium, a thin layer of cells lining blood vessels in various organs of the body, for instance.

“This is not just a virus pneumonia,” Ruschitzka, who was not involved in the latest study, tells The Scientist, referring to COVID-19. “This is a disease like we have never seen before—it is not an influenza, it hits the vessels all over, it hits the heart as well.”

To uncover the locations of cells bearing ACE2 and TMPRSS2, the preprint researchers turned to the Human Cell Atlas, a project that has allowed scientists to pool together data on human cells since 2016.

By scouring single-cell sequencing records of around 1.2 million individual cells from human tissue samples, the team was able to find out which of those cells produce both ACE2 and TMPRSS2, and note their locations in the body. The analysis used 16 unpublished datasets of lung and airway cells and 91 published datasets spanning a range of human organs.

Coauthor Christoph Muus, a graduate student at Harvard University and the Broad Institute, explains that while the data show cells in many locations in the body produce SARS-CoV-2 receptors, it’s not certain that the virus can infect all of those tissues.

“Expressing the receptor is a necessary condition but not necessarily a sufficient condition,” he says. For example, potential target cells were found in the testes, but scientists still don’t know if SARS-CoV-2 infects and replicates in that part of the body.

Jeremy Kamil, a virologist at Louisiana State University Health Shreveport, says the preprint provides important details about the human body that may help scientists understand how SARS-CoV-2 infects hosts. By finding viral protein fragments in tissue samples from patients who died because of COVID-19, scientists might be able to firm up which organs are genuine sites of infection, he adds.

“I’d say this paper gives people a roadmap at where you might want to look in the body to understand where this virus is going,” he says.

One limitation of the work is that relatively little metadata about the people who donated tissue samples were available for the various datasets, though information about age and gender were included in many. The researchers don’t know, for example, whether there was an ethnicity bias in the data, whether patients had pre-existing conditions, or whether they were taking any medications. All of these things could affect gene expression in particular cells.

Smoking status was available for a subset of the data, and the team used this to show that smoking is correlated with a greater expression of the ACE2 gene in the upper airway, but lower expression in certain lung cells. Further research is needed to understand whether this affects smokers’ susceptibility to COVID-19. Data from China suggest that smokers are 14 times more likely to develop a severe form of the disease.

Some researchers from the same group using similar data have also recently published papers in Cell and Nature. In those cases, the researchers focused on certain groups of cells. The study reported in Nature examined cells potentially involved in viral transmission and found that nasal epithelial cells, in particular, were associated with expression of ACE2 and TMPRSS2. The authors report that the virus might exploit cells that secrete fluids in the nasal passage, which might help it spread from one person to another in droplets released, say, when someone sneezes.

The Cell study, meanwhile, also found ACE2 and TMPRSS2 transcripts in nasal, gut, and lung cells but the researchers also found that the protein interferon activated ACE2 expression in vitro. The human body uses interferon to fight infections, so it is not clear whether the protein is of overall benefit or detriment to COVID-19 patients.

The use of so many different data sources backs up the validity of the preprint authors’ findings, says Marta Gaglia, a molecular biologist at Tufts University. She agrees with the researchers that discovering ACE2- and TMPRSS2-producing cells in various places around the body does not prove the virus can always infect such cells.

“I think the reality is that most of the problems come from the lung,” she adds. Plus, while doctors treating COVID-19 patients may detect problems in multiple organs, those issues might not necessarily be caused directly by SARS-CoV-2 infection, says Gaglia. A problematic immune system response, for instance, could damage certain tissues in the body as an indirect consequence of viral infection.

https://www.the-scientist.com/news-opinion/receptors-for-sars-cov-2-present-in-wide-variety-of-human-cells-67496?utm_campaign=TS_DAILY%20NEWSLETTER_2020&utm_source=hs_email&utm_medium=email&utm_content=87213170&_hsenc=p2ANqtz-_vGzY0JSZbqON-CbrWnU2wp22vNPAa-zcPDPoSZR69MA0qXhi3ukYIXekJJKZ_A_GfMi8lV1cuO5y2DnnkhV-rdYFrPQ&_hsmi=87213170

by MARY JO DILONARDO

How you move and how you eat could have an impact on how your body responds when faced with the coronavirus. Like so many other health complications, diet and exercise seem to affect the body’s ability to fight COVID-19 — the disease caused by the coronavirus — and its complications.

Exercise and COVID-19 complications

Regular exercise may help reduce the risk of acute respiratory distress syndrome (ARDS), a dangerous and potentially fatal condition caused by COVID-19, according to new research.

ARDS results when fluid builds up in in the tiny air sacs in the lungs, according to the Mayo Clinic. When this happens, lungs aren’t able to fill completely because of the fluid. That means less oxygen reaches the bloodstream, so organs don’t have enough oxygen to function.

Zhen Yan of the University of Virginia School of Medicine says medical research findings “strongly support” the possibility that exercise can prevent or at least reduce the severity of ARDS. Between 3% to 17% of all people with COVID-19 develop ARDS, according to the Centers for Disease Control and Prevention (CDC). An estimated 20% to 42% of hospitalized COVID-19 patients will develop ARDS. The range for patients admitted to intensive care is 67% to 85%.

According to earlier research, ARDS has a mortality rate as high as 45% for severe cases.

“All you hear now is either social distancing or ventilator, as if all we can do is either avoid exposure or rely on a ventilator to survive if we get infected,” Yan said in a statement. “The flip side of the story is that approximately 80% of confirmed COVID-19 patients have mild symptoms with no need of respiratory support. The question is, ‘Why?’ Our findings about an endogenous antioxidant enzyme provide important clues and have intrigued us to develop a novel therapeutic for ARDS caused by COVID-19.”

Yan, the director of the Center for Skeletal Muscle Research at UVA’s Robert M. Berne Cardiovascular Research Center, reviewed medical research of an antioxidant known as extracellular superoxide dismutase (EcSOD). The antioxidant protects tissues from damage and increases healing. It’s naturally made by muscles, but production is increased during cardiovascular exercise. The results of the findings were published in Redox Biology.
According to Yan’s analysis, even just one workout session can increase production of the antioxidant. So, he’s encouraging people to find a way to exercise while making sure to maintain social distancing.

“We cannot live in isolation forever,” he said. “Regular exercise has far more health benefits than we know. The protection against this severe respiratory disease condition is just one of the many examples.”

How diet impacts coronavirus risk

In addition to exercise, diet plays a key role in how our bodies respond to the coronavirus. We know that underlying conditions are what make so many people susceptible to COVID-19. Those with obesity, Type 2 diabetes, heart disease or high blood pressure are at the highest risk. Many of these conditions are impacted by diet.

But it’s not just making a few smart food choices once in a while. It’s a complete lifestyle change that can be affected by everything from where and how you live to culture, resources and habits.

“Healthy living is very difficult for Americans facing relentless advertising for processed and unhealthy foods, addictive (salt and sugar) ultra-processed food, entrenched and culturally-reinforced taste preferences, limited access to healthy foods for many Americans, public policy that subsidizes disease-promoting foods, sedentary behavior, and a health care and medical education system that still largely emphasizes sick care over prevention,” writes Casey Means, M.D., a practicing physician with a clinical focus on nutrition, nutrigenomics and disease prevention, and Grady Means, a writer and former corporate strategy consultant, in The Hill.

Poor diet is “now the leading cause of poor health in the U.S.,” Dr. Dariush Mozaffarian, dean of the Freidman School of Nutrition Science and Policy at Tufts University, told Jane E. Brody of The New York Times. Fewer than one American adult in five is metabolically healthy, he said.

“Only 12 percent of Americans are without high blood pressure, high cholesterol, diabetes or pre-diabetes,” he said. “The statistics are horrifying, but unlike COVID they happened gradually enough that people just shrugged their shoulders. However, beyond age, these are the biggest risk factors for illness and death from COVID-19.”

Metabolic syndrome is a cluster of conditions including high blood pressure, high blood glucose, poor cholesterol, high triglycerides and excess abdominal fat, according to the American Heart Association. Metabolic health and the immune system influence each other. When the former is lacking, infections can increase.

Many people are turning to unhealthy comfort foods during this crisis. Others are limited in what they can find because of empty store shelves. But the biggest problem is those who live in food deserts and poor communities that never had access to healthy foods in the first place.

“The COVID pandemic has cast a glaring light on longstanding costly and life-threatening inequities in American society. Those living in economically challenged communities, and especially people of color, are bearing the heaviest burden of COVID-19 infections. But while diet-related disorders increase vulnerability to the virus, limited national attention has been paid to lack of access to nutritionally wholesome foods that can sustain metabolic health and support a vigorous immune system,” Brody writes.

“Clearly, when this pandemic subsides, a lot more attention to the American diet will be needed to ward off future medical, economic and social calamities from whatever pathogen next comes down the pike.”

https://www.mnn.com/health/fitness-well-being/stories/how-exercise-and-diet-affect-coronavirus-risk-and-complications?utm_source=Weekly+Newsletter&utm_campaign=7e2aecbd8c-RSS_EMAIL_CAMPAIGN_MON0427_2020&utm_medium=email&utm_term=0_fcbff2e256-7e2aecbd8c-40844241


The unprecedented explosion of video calling in response to the pandemic has launched an unofficial social experiment.

BY JULIA SKLAR

JODI EICHLER-LEVINE FINISHED teaching a class over Zoom on April 15, and she immediately fell asleep in the guest bedroom doubling as her office. The religion studies professor at Lehigh University in Pennsylvania says that while teaching is always exhausting, she has never “conked out” like that before.

Until recently, Eichler-Levine was leading live classes full of people whose emotions she could easily gauge, even as they navigated difficult topics—such as slavery and the Holocaust—that demand a high level of conversational nuance and empathy. Now, like countless people around the world, the COVID-19 pandemic has thrust her life into a virtual space. In addition to teaching remotely, she’s been attending a weekly department happy hour, an arts-and-crafts night with friends, and a Passover seder—all over the videoconferencing app Zoom. The experience is taking a toll.

“It’s almost like you’re emoting more because you’re just a little box on a screen,” Eichler-Levine says. “I’m just so tired.”

So many people are reporting similar experiences that it’s earned its own slang term, Zoom fatigue, though this exhaustion also applies if you’re using Google Hangouts, Skype, FaceTime, or any other video-calling interface. The unprecedented explosion of their use in response to the pandemic has launched an unofficial social experiment, showing at a population scale what’s always been true: virtual interactions can be extremely hard on the brain.

“There’s a lot of research that shows we actually really struggle with this,” says Andrew Franklin, an assistant professor of cyberpsychology at Virginia’s Norfolk State University. He thinks people may be surprised at how difficult they’re finding video calls given that the medium seems neatly confined to a small screen and presents few obvious distractions.

Zoom gloom

Humans communicate even when they’re quiet. During an in-person conversation, the brain focuses partly on the words being spoken, but it also derives additional meaning from dozens of non-verbal cues, such as whether someone is facing you or slightly turned away, if they’re fidgeting while you talk, or if they inhale quickly in preparation to interrupt.

These cues help paint a holistic picture of what is being conveyed and what’s expected in response from the listener. Since humans evolved as social animals, perceiving these cues comes naturally to most of us, takes little conscious effort to parse, and can lay the groundwork for emotional intimacy.

However, a typical video call impairs these ingrained abilities, and requires sustained and intense attention to words instead. If a person is framed only from the shoulders up, the possibility of viewing hand gestures or other body language is eliminated. If the video quality is poor, any hope of gleaning something from minute facial expressions is dashed.

“For somebody who’s really dependent on those non-verbal cues, it can be a big drain not to have them,” Franklin says. Prolonged eye contact has become the strongest facial cue readily available, and it can feel threatening or overly intimate if held too long.

Multi-person screens magnify this exhausting problem. Gallery view—where all meeting participants appear Brady Bunch-style—challenges the brain’s central vision, forcing it to decode so many people at once that no one comes through meaningfully, not even the speaker.

“We’re engaged in numerous activities, but never fully devoting ourselves to focus on anything in particular,” says Franklin. Psychologists call this continuous partial attention, and it applies as much to virtual environments as it does to real ones. Think of how hard it would be to cook and read at the same time. That’s the kind of multi-tasking your brain is trying, and often failing, to navigate in a group video chat.

This leads to problems in which group video chats become less collaborative and more like siloed panels, in which only two people at a time talk while the rest listen. Because each participant is using one audio stream and is aware of all the other voices, parallel conversations are impossible. If you view a single speaker at a time, you can’t recognize how non-active participants are behaving—something you would normally pick up with peripheral vision.

For some people, the prolonged split in attention creates a perplexing sense of being drained while having accomplished nothing. The brain becomes overwhelmed by unfamiliar excess stimuli while being hyper-focused on searching for non-verbal cues that it can’t find.

That’s why a traditional phone call may be less taxing on the brain, Franklin says, because it delivers on a small promise: to convey only a voice.

Zoom boon

By contrast, the sudden shift to video calls has been a boon for people who have neurological difficulty with in-person exchanges, such as those with autism who can become overwhelmed by multiple people talking.

John Upton, an editor at the New Jersey-based news outlet Climate Central, recently found out he is autistic. Late last year, he was struggling with the mental load of attending packed conferences, engaging during in-person meetings, and navigating the small-talk that’s common in work places. He says these experiences caused “an ambiguous tension, a form of anxiety.”

As a result, he suffered a bout of autistic burnout and struggled to process complicated information—which he says is normally his strength—leading to feelings of helplessness and futility. To combat the issue, he began transitioning to working mostly from home and stacking all in-person meetings on Thursdays, to get them out of the way.

Now that the pandemic has pushed his coworkers to be remote as well, he has observed their video calls lead to fewer people talking and less filler conversation at the beginning and end of each meeting. Upton says his sense of tension and anxiety has been reduced to the point of being negligible.

This outcome is supported by research, says the University of Québec Outaouais’s Claude Normand, who studies how people with developmental and intellectual disabilities socialize online. People with autism tend to have difficulty understanding when it’s their turn to speak in live conversations, she notes. That’s why the frequent lag between speakers on video calls may actually help some autistic people. “When you’re Zooming online, it’s clear whose turn it is to talk,” Normand says.

However, other people on the autism spectrum may still struggle with video chatting, as it can exacerbate sensory triggers such as loud noise and bright lights, she adds.

On the whole, video chatting has allowed human connections to flourish in ways that would have been impossible just a few years ago. These tools enable us to maintain long-distance relationships, connect workrooms remotely, and even now, in spite of the mental exhaustion they can generate, foster some sense of togetherness during a pandemic.

It’s even possible Zoom fatigue will abate once people learn to navigate the mental tangle video chatting can cause. If you’re feeling self-conscious or overstimulated, Normand recommends you turn off your camera. Save your energy for when you absolutely want to perceive the few non-verbal cues that do come through, such as during the taxing chats with people you don’t know very well, or for when you want the warm fuzzies you get from seeing someone you love. Or if it’s a work meeting that can be done by phone, try walking at the same time.

“Walking meetings are known to improve creativity, and probably reduce stress as well,” Normand says.

https://www.nationalgeographic.com/science/2020/04/coronavirus-zoom-fatigue-is-taxing-the-brain-here-is-why-that-happens/


June Almeida with her electron microscope at the Ontario Cancer Institute in Toronto in 1963

The woman who discovered the first human coronavirus was the daughter of a Scottish bus driver, who left school at 16.

June Almeida went on to become a pioneer of virus imaging, whose work has come roaring back into focus during the present pandemic.

Covid-19 is a new illness but it is caused by a coronavirus of the type first identified by Dr Almeida in 1964 at her laboratory in St Thomas’s Hospital in London.

The virologist was born June Hart in 1930 and grew up in a tenement near Alexandra Park in the north east of Glasgow.

She left school with little formal education but got a job as a laboratory technician in histopathology at Glasgow Royal Infirmary.

Later she moved to London to further her career and in 1954 married Enriques Almeida, a Venezuelan artist.

Common cold research
The couple and their young daughter moved to Toronto in Canada and, according to medical writer George Winter, it was at the Ontario Cancer Institute that Dr Almeida developed her outstanding skills with an electron microscope.

She pioneered a method which better visualised viruses by using antibodies to aggregate them.

Mr Winter told Drivetime on BBC Radio Scotland her talents were recognised in the UK and she was lured back in 1964 to work at St Thomas’s Hospital Medical School in London, the same hospital that treated Prime Minister Boris Johnson when he was suffering from the Covid-19 virus.

On her return, she began to collaborate with Dr David Tyrrell, who was running research at the common cold unit in Salisbury in Wiltshire.

Mr Winter says Dr Tyrrell had been studying nasal washings from volunteers and his team had found that they were able to grow quite a few common cold-associated viruses but not all of them.

One sample in particular, which became known as B814, was from the nasal washings of a pupil at a boarding school in Surrey in 1960.

They found that they were able to transmit common cold symptoms to volunteers but they were unable to grow it in routine cell culture.

However, volunteer studies demonstrated its growth in organ cultures and Dr Tyrrell wondered if it could be seen by an electron microscope.

They sent samples to June Almeida who saw the virus particles in the specimens, which she described as like influenza viruses but not exactly the same.

She identified what became known as the first human coronavirus.


Coronaviruses are a group of viruses that have a halo or crown-like (corona) appearance when viewed under a microscope.

Mr Winter says that Dr Almeida had actually seen particles like this before while investigating mouse hepatitis and infectious bronchitis of chickens.

However, he says her paper to a peer-reviewed journal was rejected “because the referees said the images she produced were just bad pictures of influenza virus particles”.

The new discovery from strain B814 was written up in the British Medical Journal in 1965 and the first photographs of what she had seen were published in the Journal of General Virology two years later.

According to Mr Winter, it was Dr Tyrrell and Dr Almeida, along with Prof Tony Waterson, the man in charge at St Thomas’s, who named it coronavirus because of the crown or halo surrounding it on the viral image.

Dr Almeida later worked at the Postgraduate Medical School in London, where she was awarded a doctorate.

She finished her career at the Wellcome Institute, where she was named on several patents in the field of imaging viruses.

After leaving Wellcome, Dr Almeida become a yoga teacher but went back into virology in an advisory role in the late 1980s when she helped take novel pictures of the HIV virus.

June Almeida died in 2007, at the age of 77.

Now 13 years after her death she is finally getting recognition she deserves as a pioneer whose work speeded up understanding of the virus that is currently spreading throughout the world.

https://www.bbc.com/news/uk-scotland-52278716

Humanity tested
Nature Biomedical Engineering (2020)Cite this article

10 Altmetric

Metricsdetails

The world needs mass at-home serological testing for antibodies elicited by SARS-CoV-2, and rapid and frequent point-of-care testing for the presence of the virus’ RNA in selected populations.

How did we end up here? Two ways. Gradually, then suddenly. Ernest Hemingway’s passage is a fitting description for humanity’s perception of the exponential growth of COVID-19 cases and deaths (Fig. 1). The worldwide spread of a highly infectious pathogen was only a matter of time, as long warned by many epidemiologists, public health experts, and influential and prominent voices, such as Bill Gates. Yet most of the world was unprepared for such a pandemic; in fact, most Western countries (prominently the United States1) fumbled their response for weeks. Singapore, Hong Kong and Taiwan have shown the world that, to contain the propagation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), governments need to quickly implement aggressive testing (by detecting the viral RNA through polymerase chain reaction (PCR)), the isolation of those infected and the tracing and quarantining of their contacts, while educating their citizens about the need for physical distancing and basic public health measures (in particular, frequent hand-washing and staying at home if feeling unwell). When outbreaks are not detected and acted upon sufficiently early, drastic physical distancing — of the sort implemented by China at the end of January and maintained for months — can eventually suppress the outbreak (Fig. 1). It is however unclear whether Western countries that have implemented strict physical-distancing measures later in their infection curve will be able to gradually release such lockdowns, let alone see their outbreaks controlled.

Fig. 1: Early mass testing and early containment measures save lives.
figure1
COVID-19 confirmed cases and deaths for selected countries in a 10-day window ending at each data point (successive data points on a line denote consecutive days). Numbers in colour are the estimated number of total PCR tests per million people up to the data point indicated; stars indicate when strict lockdowns were enacted. Deaths lag with respect to confirmed cases, according to the estimated two-to-three week interval10 between the onset of symptoms and death. Case fatality rates — that is, the fractions of total confirmed cases that become deaths — mostly depend on the extent of testing, on the capacity of a country’s healthcare system, on its demographics and on the availability of drugs that can significantly dampen the severity of COVID-19 in those infected. Even with mass testing, the case fatality rate of COVID-19 is expected to be a multiple of that for seasonal flu in the United States (0.1%). Countries that deployed tests for detecting SARS-CoV-2 RNA early and widely (such as South Korea), that applied contact tracing and targeted physical distancing measures for detected cases (such as South Korea and Japan), or that enacted early, strict lockdowns (such as China) are more likely to contain the disease outbreak earlier. In fact, Singapore, Hong Kong and Taiwan have contained COVID-19 outbreaks and have managed to limit COVID-19-related deaths to less than 10 (hence, these countries are not included in the figure). Data updated 6 April 2020. Individual data points can be affected by reporting errors and delays, by wilful underreporting and by location-specific definitions (and changes to them) for confirmed cases and deaths. Data sources: European Center for Disease Control and Prevention11 (cases and deaths); Our World in Data12, various government sources (tests). A regularly updated version of this graph is available13.

Full size image
Such non-pharmacological interventions aim to ‘flatten’ the infection curve by reducing the number of transmission chains and thus the virus’ basic reproduction number — that is, the average number of new cases generated by a case in an immunologically naive population. In the absence of a safe and effective vaccine — which, if current efforts end up being successful, is unlikely to become widely available within the next two years — non-pharmacological interventions will need to remain in place to reduce the threat of secondary outbreaks by maintaining the basic reproduction number below 1. However, the type and degree of the interventions could be better tailored if governments knew who are currently infected and who have been infected and recovered. For this, the world needs to see the mass deployment of serological testing for SARS-CoV-2 antibodies (which appear to be highly specific2), and frequent testing for SARS-CoV-2 RNA in those likely to be exposed to the virus (especially healthcare workers) or at a higher risk for severe respiratory disease (such as the elderly and younger individuals with relevant comorbidities).

Medical-device companies and government and research laboratories around the world have rushed to adapt and scale up nucleic acid tests (mostly employing PCR, but also CRISPR-based detection and loop-mediated isothermal amplification) to detect the virus’ RNA, and government agencies are scrambling to assess them via emergency routes (such as the Emergency Use Authorization program3 by the United States Food and Drug Administration (FDA)). Point-of-care PCR kits — based on lateral-flow technology or cartridge-based instruments for sample preparation, nucleic acid amplification and detection — also require RNA extraction from nasal or throat swabs (or both) but can speed up the time-to-result from a few hours to roughly 30 minutes4 (and in one test, positive results can be obtained in five minutes5), with near-perfect sensitivity and specificity if sample acquisition and preparation and device operation are carried out appropriately by trained personnel. This limits the usefulness of these kits for at-home use, which would significantly raise the fraction of false negatives. Immunoassays incorporating monoclonal antibodies specific for SARS-CoV-2 antigens (for instance, a domain of the virus’ spike protein) should be amenable to home use, yet they are more difficult to develop (the antibodies are typically obtained via the immunization of transgenic animals) and are less accurate than nucleic acid testing.

Lateral flow immunoassays (akin to the pregnancy test) and enzyme-linked immunosorbent assays to detect antibodies elicited by the virus are also being rapidly developed (mostly by Chinese companies thus far). Tens of at-home lateral-flow devices6 are already being commercialized, having obtained the European Union’s CE mark or been authorized for emergency use by the FDA or the Chinese FDA. In many of these kits, the recombinant viral antigens bind to SARS-CoV-2-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) within 15 min; hence, these tests can also detect early-stage infection (of which IgM levels are a marker), but at the expense of sensitivity and accuracy (which can exceed 90% and 99% for IgG7. The real-world performance of such serology tests, which is currently unknown, will depend on the actual prevalence of COVID-19 in the population. For example, at a 5% pre-test probability of having the disease, a test with 99% sensitivity and 95% specificity would lead to as many true positives as false positives. Hence, before wide deployment, governments need to ensure that these finger-prick antibody tests are clinically validated8.

The world should roll out both antibody and nucleic acid tests on a wide scale. Widely available and inexpensive serological testing would help governments to tailor non-pharmacological interventions to specific locations and populations, to decide when to relax them and to permit citizens immune to the virus to help those who remain susceptible to it. Mass testing would also provide valuable data to pressing unknowns: what are the infection rates across locations and populations? What fraction of the population is immune? How long does immunity last and how does it depend on age and on the severity of infection? Wider deployment of nucleic acid tests would also provide clues about the prevalence of a wider range of COVID-19 symptoms, the role of children in spreading the disease, and the epidemiological characteristics of superspreaders9 and of those who were infected and asymptomatic. Testing should be complemented by privacy-minded digital surveillance, via phone apps, aiding contact tracing and permitting lighter levels of physical distancing — as done in Singapore, South Korea and Taiwan. The downside is that any invasion of privacy via the tracking of people can last longer than necessary. De-identified and aggregated health data, such as heart rate and activity levels collected via commercial wearables, might also predict (https://detectstudy.org) the emergence and location of outbreaks.

In our globalized world, the risk of further waves of COVID-19 outbreaks, and thus of prolonged drastic economic consequences, will remain substantial as long as any outbreak anywhere remains. It is in the world’s best interest that richer countries provide test kits, technical and public-health knowledge, personnel, personal protective equipment and, eventually, the necessary vaccine doses to poorer countries to assist them in their efforts to reduce and contain the spread of SARS-CoV-2. This is humanity’s next test.

References
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Shear, M. D. et al. The lost month: how a failure to test blinded the U.S. to Covid-19. The New York Times https://www.nytimes.com/2020/03/28/us/testing-coronavirus-pandemic.html (2020).

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3.
Emergency Use Authorization (U.S. Food & Drug Administration, 2020); https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations

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SARS-CoV-2 Diagnostic Pipeline (Find, 2020); https://www.finddx.org/covid-19/pipeline/

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COVID-19 Coronavirus rapid test casette. SureScreen Diagnostics https://www.surescreen.com/products/covid-19-coronavirusrapid-test-cassette (2020).

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The Associated Press. Virus test results in minutes? Scientists question accuracy. The New York Times https://www.nytimes.com/aponline/2020/03/27/world/europe/bc-virus-outbreakscramble-for-tests.html (2020).

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Hu, K. et al. Preprint at https://doi.org/10.1101/2020.03.19.20026245 (2020).

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https://www.nature.com/articles/s41551-020-0553-6?utm_source=Nature+Briefing&utm_campaign=5907ab71f9-briefing-dy-20200408&utm_medium=email&utm_term=0_c9dfd39373-5907ab71f9-44039353

The “baile funk” dance parties have been called off. Some open-air drug markets are closed for business. Gangs and militias have imposed strict curfews. Coronavirus is coming, and Rio de Janeiro’s lawless favelas are gearing up for the onslaught.

City of God, a sprawling complex of slums made famous in a hit 2002 movie of the same name, registered the first confirmed case of coronavirus in Rio’s favelas over the weekend.

Now, with the state government woefully underfunded and Brazilian President Jair Bolsonaro widely criticized for a slow response to the outbreak, criminal gangs that have long held sway across Rio’s favelas are taking their own precautions against the virus, according to residents and press reports.

According to well-sourced Rio newspaper Extra, City of God gangsters have been driving round the slum, blaring out a recorded message to residents.

“We’re imposing a curfew because nobody is taking this seriously,” the message said, according to Extra’s Tuesday story. “Whoever is in the street screwing around or going for a walk will receive a corrective and serve as an example. Better to stay home doing nothing. The message has been given.”

Reuters was unable to confirm the veracity of the recorded message, but City of God residents, who declined to give their names for fear of retribution, confirmed an evening curfew and other restrictions.

The gangs’ concern over the outbreak echoes fears nationwide about the fate of Brazil’s nearly 15 million favela residents confronting what some have dubbed “the disease of the rich.”

The coronavirus landed in the country with wealthier Brazilians returning from Europe, but is quickly migrating into poorer communities, where crowded quarters, informal labor and weak public services threaten to accelerate its spread.

Drug gangs or rival paramilitaries often act as de facto authorities in the favelas. With little or no government presence in the neighborhoods, gangs enforce social contracts. They also engage in regular shootouts with each other and police forces.

Across Brazil, some 40 million people lack access to the public water supply, while 100 million – nearly half the population – live without a connection to sewage treatment, according to the country’s National Water Agency.

“Basic sanitation is terrible,” said Jefferson Maia, a 27-year-old resident of the City of God. “Sometimes, we don’t even have water to wash our hands properly. We are very concerned with the coronavirus issue.”

Thamiris Deveza, a family doctor working in Rio’s Alemao complex of slums, said residents had been complaining for the last two weeks about a lack of water in their homes, making it difficult for them to clean their hands and protect themselves from the fast-spreading virus.

She said many pharmacies in the neighborhoods had run out of hand sanitizer. When available, it was prohibitively expensive.

FAST SPREAD

Coronavirus cases are expanding quickly in Brazil. The country had 2,201 confirmed cases on Tuesday, with 46 related deaths, according to the Health Ministry.

Rio state, where around a fifth of the population lives in favelas, now has 305 cases. Governor Wilson Witzel warned on Friday that the state’s public health system was in danger of “collapse” within 15 days.

Rio Mayor Marcelo Crivella has said that officials will deposit free soap at entrances of the city’s favelas and relocate older people with health problems to hotels. The city has already signed a deal to secure 400 rooms, he said.

“Those most at risk need to be protected as soon as possible,” Crivella told journalists on Saturday.

On Tuesday, Rio’s urban sanitation unit Comlurb kicked off a more comprehensive cleaning of some of the city’s most transited areas, including around hospitals, the mayor added.

But the favelas are still likely to be a major public health challenge, said Edmilson Migowski, an infectologist at Rio’s Federal University.

“The entry of the coronavirus into denser, less planned and less culturally assisted areas could be devastating,” he said. “Where water, soap and detergent are lacking, it will be difficult to stop the spread.”

https://www.reuters.com/article/us-health-coronavirus-brazil-favelas-fea/gangs-call-curfews-as-coronavirus-hits-rio-favelas-idUSKBN21B3EV?utm_source=NSDAY&utm_campaign=8ea0a51a66-EMAIL_CAMPAIGN_2020_03_25_04_56&utm_medium=email&utm_term=0_1254aaab7a-8ea0a51a66-374123611

Hospitals in New York City are gearing up to use the blood of people who have recovered from COVID-19 as a possible antidote for the disease. Researchers hope that the century-old approach of infusing patients with the antibody-laden blood of those who have survived an infection will help the metropolis — now the US epicentre of the outbreak — to avoid the fate of Italy, where intensive-care units (ICUs) are so crowded that doctors have turned away patients who need ventilators to breathe.

The efforts follow studies in China that attempted the measure with plasma — the fraction of blood that contains antibodies, but not red blood cells — from people who had recovered from COVID-19. But these studies have reported only preliminary results so far. The convalescent-plasma approach has also seen modest success during past severe acute respiratory syndrome (SARS) and Ebola outbreaks — but US researchers are hoping to increase the value of the treatment by selecting donor blood that is packed with antibodies and giving it to the patients who are most likely to benefit.

A key advantage to convalescent plasma is that it’s available immediately, whereas drugs and vaccines take months or years to develop. Infusing blood in this way seems to be relatively safe, provided that it is screened for viruses and other infectious agents. Scientists who have led the charge to use plasma want to deploy it now as a stopgap measure, to keep serious infections at bay and hospitals afloat as a tsunami of cases comes crashing their way.

“Every patient that we can keep out of the ICU is a huge logistical victory because there are traffic jams in hospitals,” says Michael Joyner, an anaesthesiologist and physiologist at the Mayo Clinic in Rochester, Minnesota. “We need to get this on board as soon as possible, and pray that a surge doesn’t overwhelm places like New York and the west coast.”

On 23 March, New York governor Andrew Cuomo announced the plan to use convalescent plasma to aid the response in the state, which has more than 25,000 infections, with 210 deaths. “We think it shows promise,” he said. Thanks to the researchers’ efforts, the US Food and Drug Administration (FDA) today announced that it will permit the emergency use of plasma for patients in need. As early as next week, at least two hospitals in New York City — Mount Sinai and Albert Einstein College of Medicine — hope to start using coronavirus-survivor plasma to treat people with the disease, Joyner says.

After this first rollout, researchers hope the use will be extended to people at a high risk of developing COVID-19, such as nurses and physicians. For them, it could prevent illness so that they can remain in the hospital workforce, which can’t afford depletion.

And academic hospitals across the United States are now planning to launch a placebo-controlled clinical trial to collect hard evidence on how well the treatment works. The world will be watching because, unlike drugs, blood from survivors is relatively cheap and available to any country hit hard by an outbreak.

Scientists assemble

Arturo Casadevall, an immunologist at Johns Hopkins University in Baltimore, Maryland, has been fighting to use blood as a COVID-19 treatment since late January, as the disease spread to other countries and no surefire therapy was in sight. Scientists refer to this measure as ‘passive antibody therapy’ because a person receives external antibodies, rather than generating an immune response themselves, as they would following a vaccination.

The approach dates back to the 1890s. One of the largest case studies occurred during the 1918 H1N1 influenza virus pandemic. More than 1,700 patients received blood serum from survivors, but it’s difficult to draw conclusions from studies that weren’t designed to meet current standards.

During the SARS outbreak in 2002–03, an 80-person trial of convalescent serum in Hong Kong found that people treated within 2 weeks of showing symptoms had a higher chance of being discharged from hospital than did those who weren’t treated. And survivor blood has been tested in at least two outbreaks of Ebola virus in Africa with some success. Infusions seemed to help most patients in a 1995 study in the Democratic Republic of the Congo, but the study was small and not placebo controlled. A 2015 trial in Guinea was inconclusive, but it didn’t screen plasma for high levels of antibodies. Casadevall suggests that the approach might have shown a higher efficacy had researchers enrolled only participants who were at an early stage of the deadly disease, and therefore were more likely to benefit from the treatment.

Casadevall corralled support for his idea through an editorial in the Wall Street Journal, published on 27 February, which urged the use of convalescent serum because drugs and vaccines take so long to develop. “I knew if I could get this into a newspaper, people would react, whereas if I put it into a science journal, I might not get the same reaction,” he says.

He sent his article to dozens of colleagues from different disciplines, and many joined his pursuit with enthusiasm. Joyner was one. Around 100 researchers at various institutes self-organized into different lanes. Virologists set about finding tests that could assess whether a person’s blood contains coronavirus antibodies. Clinical-trial specialists thought about how to identify and enroll candidates for treatment. Statisticians created data repositories. And, to win regulatory clearance, the group shared documents required for institutional ethical-review boards and the FDA.

Tantalizing signs

Their efforts paid off. The FDA’s classification today of convalescent plasma as an ‘investigational new drug’ against coronavirus allows scientists to submit proposals to test it in clinical trials, and lets doctors use it compassionately to treat patients with serious or life-threatening COVID-19 infections, even though it is not yet approved.

“This allows us to get started,” says Joyner. Physicians can now decide whether to offer the therapy to people with very advanced disease, or to those that seem to be headed there — as he and other researchers recommend. He says hospitals will file case reports so that the FDA gets a handle on which approaches work best.

Researchers have also submitted to the FDA three protocols for placebo-controlled trials to test the plasma, which they hope will take place at hospitals affiliated with Johns Hopkins, the Mayo Clinic and Washington University in St. Louis, along with other universities that want to take part.

Future directions

The US tests of convalescent plasma aren’t the first. Since early February, researchers in China — where the coronavirus emerged late last year — have launched several studies using the plasma. Researchers have yet to report on the status and results of these studies. But Liang Yu, an infectious-disease specialist at Zhejiang University School of Medicine in China, told Nature that in one preliminary study, doctors treated 13 people who were critically ill with COVID-19 with convalescent plasma. Within several days, he says the virus no longer seemed to be circulating in the patients, indicating that antibodies had fought it off. But he says that their conditions continued to deteriorate, suggesting that the disease might have been too far along for this therapy to be effective. Most had been sick for more than two weeks.

In one of three proposed US trials, Liise-anne Pirofski, an infectious-disease specialist at Albert Einstein College of Medicine, says researchers plan to infuse patients at an early stage of the disease and see how often they advance to critical care. Another trial would enrol severe cases. The third would explore plasma’s use as a preventative measure for people in close contact with those confirmed to have COVID-19, and would evaluate how often such people fall ill after an infusion compared with others who were similarly exposed but not treated. These outcomes are measurable within a month, she says. “Efficacy data could be obtained very, very quickly.”

Even if it works well enough, convalescent serum might be replaced by modern therapies later this year. Research groups and biotechnology companies are currently identifying antibodies against the coronavirus, with plans to develop these into precise pharmaceutical formulas. “The biotech cavalry will come on board with isolating antibodies, testing them, and developing into drugs and vaccines, but that takes time,” says Joyner.

In some ways, Pirofski is reminded of the urgency she felt as a young doctor at the start of the HIV epidemic in the early 1980s. “I met with medical residents last week, and they are so frightened of this disease, and they don’t have enough protective equipment, and they are getting sick or are worried about getting sick,” she says. A tool to help to protect them now would be welcomed.

Since becoming involved with the push for blood as a treatment, Pirofski says another aspect of the therapy holds her interest: unlike a pharmaceutical product bought from companies, this treatment is created by people who have been infected. “I get several e-mails a day from people who say, ‘I survived and now I want to help other people’,” she says. “All of these people are willing to put on their boots and brush their teeth, and come help us do this.”

https://www.nature.com/articles/d41586-020-00895-8?utm_source=fbk_nnc&utm_medium=social&utm_campaign=naturenews&fbclid=IwAR08dlcqj_ixR5eJxFxrlI4UikMrTpBLLA4_aYTxfD5CfjRLi8lli2DB3gI&utm_source=Nature+Briefing&utm_campaign=7fdc8b2aa7-briefing-dy-20200325&utm_medium=email&utm_term=0_c9dfd39373-7fdc8b2aa7-44039353


Viruses like the novel coronavirus are shells holding genetic material

As the novel coronavirus causing COVID-19 spreads across the globe, with cases surpassing 284,000 worldwide today (March 20), misinformation is spreading almost as fast.

One persistent myth is that this virus, called SARS-CoV-2, was made by scientists and escaped from a lab in Wuhan, China, where the outbreak began.

A new analysis of SARS-CoV-2 may finally put that latter idea to bed. A group of researchers compared the genome of this novel coronavirus with the seven other coronaviruses known to infect humans: SARS, MERS and SARS-CoV-2, which can cause severe disease; along with HKU1, NL63, OC43 and 229E, which typically cause just mild symptoms, the researchers wrote March 17 in the journal Nature Medicine.

“Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus,” they write in the journal article.

Kristian Andersen, an associate professor of immunology and microbiology at Scripps Research, and his colleagues looked at the genetic template for the spike proteins that protrude from the surface of the virus. The coronavirus uses these spikes to grab the outer walls of its host’s cells and then enter those cells. They specifically looked at the gene sequences responsible for two key features of these spike proteins: the grabber, called the receptor-binding domain, that hooks onto host cells; and the so-called cleavage site that allows the virus to open and enter those cells.

That analysis showed that the “hook” part of the spike had evolved to target a receptor on the outside of human cells called ACE2, which is involved in blood pressure regulation. It is so effective at attaching to human cells that the researchers said the spike proteins were the result of natural selection and not genetic engineering.

Here’s why: SARS-CoV-2 is very closely related to the virus that causes severe acute respiratory syndrome (SARS), which fanned across the globe nearly 20 years ago. Scientists have studied how SARS-CoV differs from SARS-CoV-2 — with several key letter changes in the genetic code. Yet in computer simulations, the mutations in SARS-CoV-2 don’t seem to work very well at helping the virus bind to human cells. If scientists had deliberately engineered this virus, they wouldn’t have chosen mutations that computer models suggest won’t work. But it turns out, nature is smarter than scientists, and the novel coronavirus found a way to mutate that was better — and completely different— from anything scientists could have created, the study found.

Another nail in the “escaped from evil lab” theory? The overall molecular structure of this virus is distinct from the known coronaviruses and instead most closely resembles viruses found in bats and pangolins that had been little studied and never known to cause humans any harm.

“If someone were seeking to engineer a new coronavirus as a pathogen, they would have constructed it from the backbone of a virus known to cause illness,” according to a statement from Scripps.

Where did the virus come from? The research group came up with two possible scenarios for the origin of SARS-CoV-2 in humans. One scenario follows the origin stories for a few other recent coronaviruses that have wreaked havoc in human populations. In that scenario, we contracted the virus directly from an animal — civets in the case of SARS and camels in the case of Middle East respiratory syndrome (MERS). In the case of SARS-CoV-2, the researchers suggest that animal was a bat, which transmitted the virus to another intermediate animal (possibly a pangolin, some scientists have said) that brought the virus to humans.

In that possible scenario, the genetic features that make the new coronavirus so effective at infecting human cells (its pathogenic powers) would have been in place before hopping to humans.

In the other scenario, those pathogenic features would have evolved only after the virus jumped from its animal host to humans. Some coronaviruses that originated in pangolins have a “hook structure” (that receptor binding domain) similar to that of SARS-CoV-2. In that way, a pangolin either directly or indirectly passed its virus onto a human host. Then, once inside a human host, the virus could have evolved to have its other stealth feature — the cleavage site that lets it easily break into human cells. Once it developed that capacity, the researchers said, the coronavirus would be even more capable of spreading between people.

All of this technical detail could help scientists forecast the future of this pandemic. If the virus did enter human cells in a pathogenic form, that raises the probability of future outbreaks. The virus could still be circulating in the animal population and might again jump to humans, ready to cause an outbreak. But the chances of such future outbreaks are lower if the virus must first enter the human population and then evolve the pathogenic properties, the researchers said.

https://www.livescience.com/coronavirus-not-human-made-in-lab.html?utm_source=Selligent&utm_medium=email&utm_campaign=15588&utm_content=20200321_Coronavirus_Infographic+&utm_term=3675605&m_i=Y78%2BcYxf2Qsne7KyAz%2Bro3S%2BCTo6VIPlVFATrnaXXtdOBEIZH%2BPO_hNXo7rq5mPCFLKyREQpjzGdZOYb2pvbuvu8nQp0tu

By Anette Breindl

The first attempt at using existing drugs to treat patients infected with SARS-CoV-2 has yielded disappointing results.

In 200 hospitalized patients with severe COVID-19, a 14-day regimen of twice-daily treatment with Kaletra/Aluvia (lopinavir/ritonavir, Abbvie Inc.) did not hasten recovery when added to the standard of care. Chinese clinicians led by Bin Cao of the National Clinical Research Center for Respiratory Diseases reported their findings in the March 19, 2020, issue of The New England Journal of Medicine.

Lopinavir is a protease inhibitor, while ritonavir increases the half-life of lopinavir by inhibiting its metabolism. The drug was tested because screening studies had flagged it as having activity against MERS-CoV, which has led to a clinical trial of a combination of Kaletra/Aluvia and interferon-beta for the treatment of MERS-CoV in the Kingdom of Saudi Arabia.

In the COVID-19 trial, 199 patients were treated, split evenly between drug and standard-of-care groups. The study’s primary endpoint, time to improvement, was the same between the two groups, both of which took 16 days to improve. Mortality and viral load at various time points were also not different.

In an editorial published alongside the paper, Lindsey Baden, of Harvard Medical School, and Eric Rubin, of the Harvard TH Chan School of Public Health, wrote that “the results for certain secondary endpoints are intriguing,” but also acknowledged that those results were hard to interpret, due to a mix of trial size, possible differences in illness severity at baseline, and the fact that the trial was randomized but not blinded.

And if certain endpoints were intriguing, others were discouraging. In particular, viral loads did not differ between the groups, tellingly so, according to Baden and Rubin. “Since the drug is supposed to act as a direct inhibitor of viral replication, the inability to suppress the viral load and the persistent detection of viral nucleic acid strongly suggest that it did not have the activity desired,” they wrote. “Thus, although some effect of the drug is possible, it was not easily observed.”

It is possible that larger trials will yet uncover an effect of Kaletra/Aluvia. But for now, perhaps the best hope is that other drugs will work better – in particular, remdesivir (Gilead Sciences Inc.), which was originally developed for Ebola virus disease, but proved less effective there than several other options.

A paper in the Jan. 10, 2020, issue of Nature Communications investigated the effects of Aluvia on MERS-CoV in mouse experiments, where it showed ho-hum effects. The authors of the Nature Communications paper reported that “prophylactic [Kaletra/Aluvia plus interferon-beta] slightly reduces viral loads without impacting other disease parameters.”

But remdesivir was more effective. “Both prophylactic and therapeutic [remdesivir] improve pulmonary function and reduce lung viral loads and severe lung pathology” in a mouse model of MERS, the authors reported.

Remdesivir is in both an NIH-sponsored clinical trial and a Japanese-Chinese trial as potential COVID-19 treatment, after a January case report of a patient who showed rapid improvement after he was treated with the drug for COVID-19.

Though the Kaletra/Aluvia trial’s results were not as hoped, Baden and Rubin noted that the trial itself was an encouraging bit of news, as well as a “heroic effort…. As we saw during the 2014 Ebola outbreak in West Africa, obtaining high-quality clinical trial data to guide the care of patients is extremely difficult in the face of an epidemic, and the feasibility of a randomized design has been called into question. Yet Cao’s group of determined investigators not only succeeded but ended up enrolling a larger number of patients (199) than originally targeted.”