Category Archives: Genetic medicine

Ayushi Agarwal, Copy Editor

On Thursday, Drug Innovation Ventures at Emory (DRIVE) submitted an Investigational New Drug (IND) application to the Food and Drug Administration (FDA) for their experimental COVID-19 treatment, EIDD-2801.

EIDD-2801 is an antiviral compound that directly attacks coronaviruses in the lungs. The compound, a nucleoside analogue, deceives the virus into attaching and injecting its genetic information into a false host.

CEO of DRIVE, director of the Emory Institute for Drug Development (EIDD) and Professor of Pharmacology George Painter (72C, 77G) and his team have been working on the oral therapy for over five years and in the past month partnered with biotechnology company Ridgeback Biotherapeutics. The original purpose behind the treatment was to combat influenza, but Painter said the medicine can also be used to treat COVID-19 and other coronavirus strains. The novel coronavirus outbreak has brought the opportunity to find a partner and accelerate FDA approval to DRIVEs process.

[Ridgeback is] well suited to us because they deal with emerging infectious disease, Painter said. At a certain point, the structure of a university really isnt the optimal place to develop a drug. There are various procedures for the university that are not very compatible with moving quickly.

Ridgeback Biotherapeutics have an exclusive license of the intellectual property over the compound. If approved by the FDA, Ridgeback can develop, commercialize and sell EIDD-2801.

DRIVE and Emory get milestone payments and royalties, Painter said. A lot of that will come back to DRIVE and be put right back into its effort to identify and develop critical medicines for unmet medical needs.

Over the past three years, Painter and his team have gathered an enormous amount of data, which they have been working on compiling in the past few months.

The IND application is titled The Use of EIDD-2801 for the Treatment of Influenza and consists of hundreds of hyperlinked research reports about the compound.

After an IND application is submitted, the FDA must respond within 30 days. However, Painter predicts that the FDA will respond sooner because of COVID-19s exigent danger. Although there is no official communication from FDA stating an accelerated approval process, Painter assured that he and his team have been in frequent contact with the FDA about their response.

Painter hopes that in three to four weeks, the treatment will be tested on patients in the form of clinical trials, off-label medicines and trial basis. EEID-2801 will first be tested on healthy volunteers and later on COVID-19 patients if initial testing succeeds.

Amid the Universitys closure, Painters lab is only allowed to operate with essential personnel. However, Painters team is carrying out critical maintenance on lab equipment.

Painter emphasized the imperative group effort of this process, stating that, a lot of people put in long hours, many more than they had to, in order to get this out the door.

A lot of credit to a lot of people, Painter said. Lets just cross our fingers and hope it works.

See the original post:
Emory Coronavirus Treatment Submitted to FDA - The Emory Wheel

Even at their most effective and draconian containment strategies have only slowed the spread of the respiratory disease Covid-19. With the World Health Organization finally declaring a pandemic, all eyes have turned to the prospect of a vaccine, because only a vaccine can prevent people from getting sick.

About 35 companies and academic institutions are racing to create such a vaccine, at least four of which already have candidates they have been testing in animals. The first of these produced by Boston-based biotech firm Moderna will enter human trials imminently.

This unprecedented speed is thanks in large part to early Chinese efforts to sequence the genetic material of Sars-CoV-2, the virus that causes Covid-19. China shared that sequence in early January, allowing research groups around the world to grow the live virus and study how it invades human cells and makes people sick.

But there is another reason for the head start. Though nobody could have predicted that the next infectious disease to threaten the globe would be caused by a coronavirus flu is generally considered to pose the greatest pandemic risk vaccinologists had hedged their bets by working on prototype pathogens. The speed with which we have [produced these candidates] builds very much on the investment in understanding how to develop vaccines for other coronaviruses, says Richard Hatchett, CEO of the Oslo-based nonprofit the Coalition for Epidemic Preparedness Innovations (Cepi), which is leading efforts to finance and coordinate Covid-19 vaccine development.

Coronaviruses have caused two other recent epidemics severe acute respiratory syndrome (Sars) in China in 2002-04, and Middle East respiratory syndrome (Mers), which started in Saudi Arabia in 2012. In both cases, work began on vaccines that were later shelved when the outbreaks were contained. One company, Maryland-based Novavax, has now repurposed those vaccines for Sars-CoV-2, and says it has several candidates ready to enter human trials this spring. Moderna, meanwhile, built on earlier work on the Mers virus conducted at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.

Sars-CoV-2 shares between 80% and 90% of its genetic material with the virus that caused Sars hence its name. Both consist of a strip of ribonucleic acid (RNA) inside a spherical protein capsule that is covered in spikes. The spikes lock on to receptors on the surface of cells lining the human lung the same type of receptor in both cases allowing the virus to break into the cell. Once inside, it hijacks the cells reproductive machinery to produce more copies of itself, before breaking out of the cell again and killing it in the process.

All vaccines work according to the same basic principle. They present part or all of the pathogen to the human immune system, usually in the form of an injection and at a low dose, to prompt the system to produce antibodies to the pathogen. Antibodies are a kind of immune memory which, having been elicited once, can be quickly mobilised again if the person is exposed to the virus in its natural form.

Traditionally, immunisation has been achieved using live, weakened forms of the virus, or part or whole of the virus once it has been inactivated by heat or chemicals. These methods have drawbacks. The live form can continue to evolve in the host, for example, potentially recapturing some of its virulence and making the recipient sick, while higher or repeat doses of the inactivated virus are required to achieve the necessary degree of protection. Some of the Covid-19 vaccine projects are using these tried-and-tested approaches, but others are using newer technology. One more recent strategy the one that Novavax is using, for example constructs a recombinant vaccine. This involves extracting the genetic code for the protein spike on the surface of Sars-CoV-2, which is the part of the virus most likely to provoke an immune reaction in humans, and pasting it into the genome of a bacterium or yeast forcing these microorganisms to churn out large quantities of the protein. Other approaches, even newer, bypass the protein and build vaccines from the genetic instruction itself. This is the case for Moderna and another Boston company, CureVac, both of which are building Covid-19 vaccines out of messenger RNA.

Cepis original portfolio of four funded Covid-19 vaccine projects was heavily skewed towards these more innovative technologies, and last week it announced $4.4m (3.4m) of partnership funding with Novavax and with a University of Oxford vectored vaccine project. Our experience with vaccine development is that you cant anticipate where youre going to stumble, says Hatchett, meaning that diversity is key. And the stage where any approach is most likely to stumble is clinical or human trials, which, for some of the candidates, are about to get under way.

Clinical trials, an essential precursor to regulatory approval, usually take place in three phases. The first, involving a few dozen healthy volunteers, tests the vaccine for safety, monitoring for adverse effects. The second, involving several hundred people, usually in a part of the world affected by the disease, looks at how effective the vaccine is, and the third does the same in several thousand people. But theres a high level of attrition as experimental vaccines pass through these phases. Not all horses that leave the starting gate will finish the race, says Bruce Gellin, who runs the global immunisation programme for the Washington DC-based nonprofit, the Sabin Vaccine Institute.

There are good reasons for that. Either the candidates are unsafe, or theyre ineffective, or both. Screening out duds is essential, which is why clinical trials cant be skipped or hurried. Approval can be accelerated if regulators have approved similar products before. The annual flu vaccine, for example, is the product of a well-honed assembly line in which only one or a few modules have to be updated each year. In contrast, Sars-CoV-2 is a novel pathogen in humans, and many of the technologies being used to build vaccines are relatively untested too. No vaccine made from genetic material RNA or DNA has been approved to date, for example. So the Covid-19 vaccine candidates have to be treated as brand new vaccines, and as Gellin says: While there is a push to do things as fast as possible, its really important not to take shortcuts.

An illustration of that is a vaccine that was produced in the 1960s against respiratory syncytial virus, a common virus that causes cold-like symptoms in children. In clinical trials, this vaccine was found to aggravate those symptoms in infants who went on to catch the virus. A similar effect was observed in animals given an early experimental Sars vaccine. It was later modified to eliminate that problem but, now that it has been repurposed for Sars-CoV-2, it will need to be put through especially stringent safety testing to rule out the risk of enhanced disease.

Its for these reasons that taking a vaccine candidate all the way to regulatory approval typically takes a decade or more, and why President Trump sowed confusion when, at a meeting at the White House on 2 March, he pressed for a vaccine to be ready by the US elections in November an impossible deadline. Like most vaccinologists, I dont think this vaccine will be ready before 18 months, says Annelies Wilder-Smith, professor of emerging infectious diseases at the London School of Hygiene and Tropical Medicine. Thats already extremely fast, and it assumes there will be no hitches.

In the meantime, there is another potential problem. As soon as a vaccine is approved, its going to be needed in vast quantities and many of the organisations in the Covid-19 vaccine race simply dont have the necessary production capacity. Vaccine development is already a risky affair, in business terms, because so few candidates get anywhere near the clinic. Production facilities tend to be tailored to specific vaccines, and scaling these up when you dont yet know if your product will succeed is not commercially feasible. Cepi and similar organisations exist to shoulder some of the risk, keeping companies incentivised to develop much-needed vaccines. Cepi plans to invest in developing a Covid-19 vaccine and boosting manufacturing capacity in parallel, and earlier this month it put out a call for $2bn to allow it to do so.

Once a Covid-19 vaccine has been approved, a further set of challenges will present itself. Getting a vaccine thats proven to be safe and effective in humans takes one at best about a third of the way to whats needed for a global immunisation programme, says global health expert Jonathan Quick of Duke University in North Carolina, author of The End of Epidemics (2018). Virus biology and vaccines technology could be the limiting factors, but politics and economics are far more likely to be the barrier to immunisation.

The problem is making sure the vaccine gets to all those who need it. This is a challenge even within countries, and some have worked out guidelines. In the scenario of a flu pandemic, for example, the UK would prioritise vaccinating healthcare and social care workers, along with those considered at highest medical risk including children and pregnant women with the overall goal of keeping sickness and death ra tes as low as possible. But in a pandemic, countries also have to compete with each other for medicines.

Because pandemics tend to hit hardest those countries that have the most fragile and underfunded healthcare systems, there is an inherent imbalance between need and purchasing power when it comes to vaccines. During the 2009 H1N1 flu pandemic, for example, vaccine supplies were snapped up by nations that could afford them, leaving poorer ones short. But you could also imagine a scenario where, say, India a major supplier of vaccines to the developing world not unreasonably decides to use its vaccine production to protect its own 1.3 billion-strong population first, before exporting any.

Outside of pandemics, the WHO brings governments, charitable foundations and vaccine-makers together to agree an equitable global distribution strategy, and organisations like Gavi, the vaccine alliance, have come up with innovative funding mechanisms to raise money on the markets for ensuring supply to poorer countries. But each pandemic is different, and no country is bound by any arrangement the WHO proposes leaving many unknowns. As Seth Berkley, CEO of Gavi, points out: The question is, what will happen in a situation where youve got national emergencies going on?

This is being debated, but it will be a while before we see how it plays out. The pandemic, says Wilder-Smith, will probably have peaked and declined before a vaccine is available. A vaccine could still save many lives, especially if the virus becomes endemic or perennially circulating like flu and there are further, possibly seasonal, outbreaks. But until then, our best hope is to contain the disease as far as possible. To repeat the sage advice: wash your hands.

This article was amended on 19 March 2020. An earlier version incorrectly stated that the Sabin Vaccine Institute was collaborating with the Coalition for Epidemic Preparedness Innovations (Cepi) on a Covid-19 vaccine.

Read more:
Coronavirus vaccine: when will it be ready? - The Guardian

At least five patients, including some doctors, have overcome the critical state of health in which they had fallen due to the coronavirus and been moved from the Intensive Care units to normal hospital wards, after undergoing an expensive treatment that is producing good results.

Of the patients who have responded adequately to treatment, there are four from Santiago: Dr. Daniel Rivera, president of the Board of Directors of the Unin Mdica Clinic, urologist Fausto Hernndez, ex-governor Jos Izquierdo and patient Juan Ramn. In Santo Domingo, the political leader of San Pedro de Macors, Senator Jos Hazim, while Dr. Felix Antonio Cruz Jiminin has presented significant improvement, although he is still in intensive care with mechanical respiration, admitted to the General Hospital of the Plaza de health.

The details were offered by the Minister of Public Health, Rafael Snchez Crdenas, on the eighth day of the virtual press conference to report the updates to the Covid-19.He said it is a non-over-the-counter medicine that is applied intravenously and is applied to critically ill patients with complicated pneumonia.

A drug used in the treatment of arthritis patients has been applied to these patients.It is tocilizumab, a biological medicine, which is supplied through the High-Cost Medicines Program of the Ministry of Public Health.

Tocilizumab (Actemra) is a biologic medication approved to treat rheumatoid arthritis (RA) in adults, polyarticular juvenile rheumatoid arthritis (JRA), and the systemic form of juvenile idiopathic arthritis (JIA) in children. It isused to suppress the immune system in autoimmune diseases.

Biological drugs are artificial and manufactured using genetic engineering techniques and are closely related to a protein that the body produces naturally.

Dr. Snchez Crdenas reported that there are nine doctors registered with the virus, of whom four were in the process of their work, and others were infected on a cruise or airplane trip, and about three nurses.

He recalled that the highest risk of death is in people over 60 years old and people with co-morbidities, so he called people to take more extreme care of older adults.

Cross-testsThe Minister of Public Health, Rafael Snchez Crdenas, announced that from yesterday the trial would begin with cross-tests at the Dr. Defill National Laboratory, in order to speed up the confirmation of Covid-19 cases.

THE PROCESSSnchez Crdenas revealed that starting today, Saturday, rapid tests of up to 15 minutes will be made, through blood collection obtained from the pulpejo, with patients who have tested positive for other types of tests, to confirm their effectiveness, and then put them into service.

The testsThe effectiveness of rapid tests can be as high as 95%, and the PCR tests, which are being applied in the laboratory, are a specific test with 95% effectiveness, said Crdenas.Those 15-minute rapid tests, of which there are already samples in the country, will be tested today with patients.

Originally posted here:
Treatment gets five out of Intensive Care - Dominican Today

Editors Note: The Atlantic is making vital coverage of the coronavirus available to all readers. Find the collection here.

Three months ago, no one knew that SARS-CoV-2 existed. Now the virus has spread to almost every country, infecting at least 446,000 people whom we know about, and many more whom we do not. It has crashed economies and broken health-care systems, filled hospitals and emptied public spaces. It has separated people from their workplaces and their friends. It has disrupted modern society on a scale that most living people have never witnessed. Soon, most everyone in the United States will know someone who has been infected. Like World War II or the 9/11 attacks, this pandemic has already imprinted itself upon the nations psyche.

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A global pandemic of this scale was inevitable. In recent years, hundreds of health experts have written books, white papers, and op-eds warning of the possibility. Bill Gates has been telling anyone who would listen, including the 18 million viewers of his TED Talk. In 2018, I wrote a story for The Atlantic arguing that America was not ready for the pandemic that would eventually come. In October, the Johns Hopkins Center for Health Security war-gamed what might happen if a new coronavirus swept the globe. And then one did. Hypotheticals became reality. What if? became Now what?

So, now what? In the late hours of last Wednesday, which now feels like the distant past, I was talking about the pandemic with a pregnant friend who was days away from her due date. We realized that her child might be one of the first of a new cohort who are born into a society profoundly altered by COVID-19. We decided to call them Generation C.

As well see, Gen Cs lives will be shaped by the choices made in the coming weeks, and by the losses we suffer as a result. But first, a brief reckoning. On the Global Health Security Index, a report card that grades every country on its pandemic preparedness, the United States has a score of 83.5the worlds highest. Rich, strong, developed, America is supposed to be the readiest of nations. That illusion has been shattered. Despite months of advance warning as the virus spread in other countries, when America was finally tested by COVID-19, it failed.

Anne Applebaum: The coronavirus called Americas bluff

No matter what, a virus [like SARS-CoV-2] was going to test the resilience of even the most well-equipped health systems, says Nahid Bhadelia, an infectious-diseases physician at the Boston University School of Medicine. More transmissible and fatal than seasonal influenza, the new coronavirus is also stealthier, spreading from one host to another for several days before triggering obvious symptoms. To contain such a pathogen, nations must develop a test and use it to identify infected people, isolate them, and trace those theyve had contact with. That is what South Korea, Singapore, and Hong Kong did to tremendous effect. It is what the United States did not.

As my colleagues Alexis Madrigal and Robinson Meyer have reported, the Centers for Disease Control and Prevention developed and distributed a faulty test in February. Independent labs created alternatives, but were mired in bureaucracy from the FDA. In a crucial month when the American caseload shot into the tens of thousands, only hundreds of people were tested. That a biomedical powerhouse like the U.S. should so thoroughly fail to create a very simple diagnostic test was, quite literally, unimaginable. Im not aware of any simulations that I or others have run where we [considered] a failure of testing, says Alexandra Phelan of Georgetown University, who works on legal and policy issues related to infectious diseases.

The testing fiasco was the original sin of Americas pandemic failure, the single flaw that undermined every other countermeasure. If the country could have accurately tracked the spread of the virus, hospitals could have executed their pandemic plans, girding themselves by allocating treatment rooms, ordering extra supplies, tagging in personnel, or assigning specific facilities to deal with COVID-19 cases. None of that happened. Instead, a health-care system that already runs close to full capacity, and that was already challenged by a severe flu season, was suddenly faced with a virus that had been left to spread, untracked, through communities around the country. Overstretched hospitals became overwhelmed. Basic protective equipment, such as masks, gowns, and gloves, began to run out. Beds will soon follow, as will the ventilators that provide oxygen to patients whose lungs are besieged by the virus.

Read: The people ignoring social distancing

With little room to surge during a crisis, Americas health-care system operates on the assumption that unaffected states can help beleaguered ones in an emergency. That ethic works for localized disasters such as hurricanes or wildfires, but not for a pandemic that is now in all 50 states. Cooperation has given way to competition; some worried hospitals have bought out large quantities of supplies, in the way that panicked consumers have bought out toilet paper.

Partly, thats because the White House is a ghost town of scientific expertise. A pandemic-preparedness office that was part of the National Security Council was dissolved in 2018. On January 28, Luciana Borio, who was part of that team, urged the government to act now to prevent an American epidemic, and specifically to work with the private sector to develop fast, easy diagnostic tests. But with the office shuttered, those warnings were published in The Wall Street Journal, rather than spoken into the presidents ear. Instead of springing into action, America sat idle.

Derek Thompson: America is acting like a failed state

Rudderless, blindsided, lethargic, and uncoordinated, America has mishandled the COVID-19 crisis to a substantially worse degree than what every health expert Ive spoken with had feared. Much worse, said Ron Klain, who coordinated the U.S. response to the West African Ebola outbreak in 2014. Beyond any expectations we had, said Lauren Sauer, who works on disaster preparedness at Johns Hopkins Medicine. As an American, Im horrified, said Seth Berkley, who heads Gavi, the Vaccine Alliance. The U.S. may end up with the worst outbreak in the industrialized world.

Having fallen behind, it will be difficultbut not impossiblefor the United States to catch up. To an extent, the near-term future is set because COVID-19 is a slow and long illness. People who were infected several days ago will only start showing symptoms now, even if they isolated themselves in the meantime. Some of those people will enter intensive-care units in early April. As of last weekend, the nation had 17,000 confirmed cases, but the actual number was probably somewhere between 60,000 and 245,000. Numbers are now starting to rise exponentially: As of Wednesday morning, the official case count was 54,000, and the actual case count is unknown. Health-care workers are already seeing worrying signs: dwindling equipment, growing numbers of patients, and doctors and nurses who are themselves becoming infected.

Italy and Spain offer grim warnings about the future. Hospitals are out of room, supplies, and staff. Unable to treat or save everyone, doctors have been forced into the unthinkable: rationing care to patients who are most likely to survive, while letting others die. The U.S. has fewer hospital beds per capita than Italy. A study released by a team at Imperial College London concluded that if the pandemic is left unchecked, those beds will all be full by late April. By the end of June, for every available critical-care bed, there will be roughly 15 COVID-19 patients in need of one. By the end of the summer, the pandemic will have directly killed 2.2 million Americans, notwithstanding those who will indirectly die as hospitals are unable to care for the usual slew of heart attacks, strokes, and car accidents. This is the worst-case scenario. To avert it, four things need to happenand quickly.

Read: All the presidents lies about the coronavirus

The first and most important is to rapidly produce masks, gloves, and other personal protective equipment. If health-care workers cant stay healthy, the rest of the response will collapse. In some places, stockpiles are already so low that doctors are reusing masks between patients, calling for donations from the public, or sewing their own homemade alternatives. These shortages are happening because medical supplies are made-to-order and depend on byzantine international supply chains that are currently straining and snapping. Hubei province in China, the epicenter of the pandemic, was also a manufacturing center of medical masks.

In the U.S., the Strategic National Stockpilea national larder of medical equipmentis already being deployed, especially to the hardest-hit states. The stockpile is not inexhaustible, but it can buy some time. Donald Trump could use that time to invoke the Defense Production Act, launching a wartime effort in which American manufacturers switch to making medical equipment. But after invoking the act last Wednesday, Trump has failed to actually use it, reportedly due to lobbying from the U.S. Chamber of Commerce and heads of major corporations.

Some manufacturers are already rising to the challenge, but their efforts are piecemeal and unevenly distributed. One day, well wake up to a story of doctors in City X who are operating with bandanas, and a closet in City Y with masks piled into it, says Ali Khan, the dean of public health at the University of Nebraska Medical Center. A massive logistics and supply-chain operation [is] now needed across the country, says Thomas Inglesby of Johns Hopkins Bloomberg School of Public Health. That cant be managed by small and inexperienced teams scattered throughout the White House. The solution, he says, is to tag in the Defense Logistics Agencya 26,000-person group that prepares the U.S. military for overseas operations and that has assisted in past public-health crises, including the 2014 Ebola outbreak.

This agency can also coordinate the second pressing need: a massive rollout of COVID-19 tests. Those tests have been slow to arrive because of five separate shortages: of masks to protect people administering the tests; of nasopharyngeal swabs for collecting viral samples; of extraction kits for pulling the viruss genetic material out of the samples; of chemical reagents that are part of those kits; and of trained people who can give the tests. Many of these shortages are, again, due to strained supply chains. The U.S. relies on three manufacturers for extraction reagents, providing redundancy in case any of them failsbut all of them failed in the face of unprecedented global demand. Meanwhile, Lombardy, Italy, the hardest-hit place in Europe, houses one of the largest manufacturers of nasopharyngeal swabs.

Read: Why the coronavirus has been so successful

Some shortages are being addressed. The FDA is now moving quickly to approve tests developed by private labs. At least one can deliver results in less than an hour, potentially allowing doctors to know if the patient in front of them has COVID-19. The country is adding capacity on a daily basis, says Kelly Wroblewski of the Association of Public Health Laboratories.

On March 6, Trump said that anyone who wants a test can get a test. That was (and still is) untrue, and his own officials were quick to correct him. Regardless, anxious people still flooded into hospitals, seeking tests that did not exist. People wanted to be tested even if they werent symptomatic, or if they sat next to someone with a cough, says Saskia Popescu of George Mason University, who works to prepare hospitals for pandemics. Others just had colds, but doctors still had to use masks to examine them, burning through their already dwindling supplies. It really stressed the health-care system, Popescu says. Even now, as capacity expands, tests must be used carefully. The first priority, says Marc Lipsitch of Harvard, is to test health-care workers and hospitalized patients, allowing hospitals to quell any ongoing fires. Only later, once the immediate crisis is slowing, should tests be deployed in a more widespread way. This isnt just going to be: Lets get the tests out there! Inglesby says.

These measures will take time, during which the pandemic will either accelerate beyond the capacity of the health system or slow to containable levels. Its courseand the nations fatenow depends on the third need, which is social distancing. Think of it this way: There are now only two groups of Americans. Group A includes everyone involved in the medical response, whether thats treating patients, running tests, or manufacturing supplies. Group B includes everyone else, and their job is to buy Group A more time. Group B must now flatten the curve by physically isolating themselves from other people to cut off chains of transmission. Given the slow fuse of COVID-19, to forestall the future collapse of the health-care system, these seemingly drastic steps must be taken immediately, before they feel proportionate, and they must continue for several weeks.

Juliette Kayyem: The crisis could last 18 months. Be prepared.

Persuading a country to voluntarily stay at home is not easy, and without clear guidelines from the White House, mayors, governors, and business owners have been forced to take their own steps. Some states have banned large gatherings or closed schools and restaurants. At least 21 have now instituted some form of mandatory quarantine, compelling people to stay at home. And yet many citizens continue to crowd into public spaces.

In these moments, when the good of all hinges on the sacrifices of many, clear coordination mattersthe fourth urgent need. The importance of social distancing must be impressed upon a public who must also be reassured and informed. Instead, Trump has repeatedly played down the problem, telling America that we have it very well under control when we do not, and that cases were going to be down to close to zero when they were rising. In some cases, as with his claims about ubiquitous testing, his misleading gaffes have deepened the crisis. He has even touted unproven medications.

Away from the White House press room, Trump has apparently been listening to Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases. Fauci has advised every president since Ronald Reagan on new epidemics, and now sits on the COVID-19 task force that meets with Trump roughly every other day. Hes got his own style, lets leave it at that, Fauci told me, but any kind of recommendation that I have made thus far, the substance of it, he has listened to everything.

Read: Grocery stores are the coronavirus tipping point

But Trump already seems to be wavering. In recent days, he has signaled that he is prepared to backtrack on social-distancing policies in a bid to protect the economy. Pundits and business leaders have used similar rhetoric, arguing that high-risk people, such as the elderly, could be protected while lower-risk people are allowed to go back to work. Such thinking is seductive, but flawed. It overestimates our ability to assess a persons risk, and to somehow wall off the high-risk people from the rest of society. It underestimates how badly the virus can hit low-risk groups, and how thoroughly hospitals will be overwhelmed if even just younger demographics are falling sick.

A recent analysis from the University of Pennsylvania estimated that even if social-distancing measures can reduce infection rates by 95 percent, 960,000 Americans will still need intensive care. There are only about 180,000 ventilators in the U.S. and, more pertinently, only enough respiratory therapists and critical-care staff to safely look after 100,000 ventilated patients. Abandoning social distancing would be foolish. Abandoning it now, when tests and protective equipment are still scarce, would be catastrophic.

Read: Americas hospitals have never experienced anything like this

If Trump stays the course, if Americans adhere to social distancing, if testing can be rolled out, and if enough masks can be produced, there is a chance that the country can still avert the worst predictions about COVID-19, and at least temporarily bring the pandemic under control. No one knows how long that will take, but it wont be quick. It could be anywhere from four to six weeks to up to three months, Fauci said, but I dont have great confidence in that range.

Even a perfect response wont end the pandemic. As long as the virus persists somewhere, theres a chance that one infected traveler will reignite fresh sparks in countries that have already extinguished their fires. This is already happening in China, Singapore, and other Asian countries that briefly seemed to have the virus under control. Under these conditions, there are three possible endgames: one thats very unlikely, one thats very dangerous, and one thats very long.

The first is that every nation manages to simultaneously bring the virus to heel, as with the original SARS in 2003. Given how widespread the coronavirus pandemic is, and how badly many countries are faring, the odds of worldwide synchronous control seem vanishingly small.

The second is that the virus does what past flu pandemics have done: It burns through the world and leaves behind enough immune survivors that it eventually struggles to find viable hosts. This herd immunity scenario would be quick, and thus tempting. But it would also come at a terrible cost: SARS-CoV-2 is more transmissible and fatal than the flu, and it would likely leave behind many millions of corpses and a trail of devastated health systems. The United Kingdom initially seemed to consider this herd-immunity strategy, before backtracking when models revealed the dire consequences. The U.S. now seems to be considering it too.

Read: What will you do if you start coughing?

The third scenario is that the world plays a protracted game of whack-a-mole with the virus, stamping out outbreaks here and there until a vaccine can be produced. This is the best option, but also the longest and most complicated.

It depends, for a start, on making a vaccine. If this were a flu pandemic, that would be easier. The world is experienced at making flu vaccines and does so every year. But there are no existing vaccines for coronavirusesuntil now, these viruses seemed to cause diseases that were mild or rareso researchers must start from scratch. The first steps have been impressively quick. Last Monday, a possible vaccine created by Moderna and the National Institutes of Health went into early clinical testing. That marks a 63-day gap between scientists sequencing the viruss genes for the first time and doctors injecting a vaccine candidate into a persons arm. Its overwhelmingly the world record, Fauci said.

But its also the fastest step among many subsequent slow ones. The initial trial will simply tell researchers if the vaccine seems safe, and if it can actually mobilize the immune system. Researchers will then need to check that it actually prevents infection from SARS-CoV-2. Theyll need to do animal tests and large-scale trials to ensure that the vaccine doesnt cause severe side effects. Theyll need to work out what dose is required, how many shots people need, if the vaccine works in elderly people, and if it requires other chemicals to boost its effectiveness.

Even if it works, they dont have an easy way to manufacture it at a massive scale, said Seth Berkley of Gavi. Thats because Moderna is using a new approach to vaccination. Existing vaccines work by providing the body with inactivated or fragmented viruses, allowing the immune system to prep its defenses ahead of time. By contrast, Modernas vaccine comprises a sliver of SARS-CoV-2s genetic materialits RNA. The idea is that the body can use this sliver to build its own viral fragments, which would then form the basis of the immune systems preparations. This approach works in animals, but is unproven in humans. By contrast, French scientists are trying to modify the existing measles vaccine using fragments of the new coronavirus. The advantage of that is that if we needed hundreds of doses tomorrow, a lot of plants in the world know how to do it, Berkley said. No matter which strategy is faster, Berkley and others estimate that it will take 12 to 18 months to develop a proven vaccine, and then longer still to make it, ship it, and inject it into peoples arms.

Read: COVID-19 vaccines are coming, but theyre not what you think

Its likely, then, that the new coronavirus will be a lingering part of American life for at least a year, if not much longer. If the current round of social-distancing measures works, the pandemic may ebb enough for things to return to a semblance of normalcy. Offices could fill and bars could bustle. Schools could reopen and friends could reunite. But as the status quo returns, so too will the virus. This doesnt mean that society must be on continuous lockdown until 2022. But we need to be prepared to do multiple periods of social distancing, says Stephen Kissler of Harvard.

Much about the coming years, including the frequency, duration, and timing of social upheavals, depends on two properties of the virus, both of which are currently unknown. First: seasonality. Coronaviruses tend to be winter infections that wane or disappear in the summer. That may also be true for SARS-CoV-2, but seasonal variations might not sufficiently slow the virus when it has so many immunologically naive hosts to infect. Much of the world is waiting anxiously to see whatif anythingthe summer does to transmission in the Northern Hemisphere, says Maia Majumder of Harvard Medical School and Boston Childrens Hospital.

Second: duration of immunity. When people are infected by the milder human coronaviruses that cause cold-like symptoms, they remain immune for less than a year. By contrast, the few who were infected by the original SARS virus, which was far more severe, stayed immune for much longer. Assuming that SARS-CoV-2 lies somewhere in the middle, people who recover from their encounters might be protected for a couple of years. To confirm that, scientists will need to develop accurate serological tests, which look for the antibodies that confer immunity. Theyll also need to confirm that such antibodies actually stop people from catching or spreading the virus. If so, immune citizens can return to work, care for the vulnerable, and anchor the economy during bouts of social distancing.

Scientists can use the periods between those bouts to develop antiviral drugsalthough such drugs are rarely panaceas, and come with possible side effects and the risk of resistance. Hospitals can stockpile the necessary supplies. Testing kits can be widely distributed to catch the viruss return as quickly as possible. Theres no reason that the U.S. should let SARS-CoV-2 catch it unawares again, and thus no reason that social-distancing measures need to be deployed as broadly and heavy-handedly as they now must be. As Aaron E. Carroll and Ashish Jha recently wrote, We can keep schools and businesses open as much as possible, closing them quickly when suppression fails, then opening them back up again once the infected are identified and isolated. Instead of playing defense, we could play more offense.

Whether through accumulating herd immunity or the long-awaited arrival of a vaccine, the virus will find spreading explosively more and more difficult. Its unlikely to disappear entirely. The vaccine may need to be updated as the virus changes, and people may need to get revaccinated on a regular basis, as they currently do for the flu. Models suggest that the virus might simmer around the world, triggering epidemics every few years or so. But my hope and expectation is that the severity would decline, and there would be less societal upheaval, Kissler says. In this future, COVID-19 may become like the flu is todaya recurring scourge of winter. Perhaps it will eventually become so mundane that even though a vaccine exists, large swaths of Gen C wont bother getting it, forgetting how dramatically their world was molded by its absence.

The cost of reaching that point, with as few deaths as possible, will be enormous. As my colleague Annie Lowrey wrote, the economy is experiencing a shock more sudden and severe than anyone alive has ever experienced. About one in five people in the United States have lost working hours or jobs. Hotels are empty. Airlines are grounding flights. Restaurants and other small businesses are closing. Inequalities will widen: People with low incomes will be hardest-hit by social-distancing measures, and most likely to have the chronic health conditions that increase their risk of severe infections. Diseases have destabilized cities and societies many times over, but it hasnt happened in this country in a very long time, or to quite the extent that were seeing now, says Elena Conis, a historian of medicine at UC Berkeley. Were far more urban and metropolitan. We have more people traveling great distances and living far from family and work.

After infections begin ebbing, a secondary pandemic of mental-health problems will follow. At a moment of profound dread and uncertainty, people are being cut off from soothing human contact. Hugs, handshakes, and other social rituals are now tinged with danger. People with anxiety or obsessive-compulsive disorder are struggling. Elderly people, who are already excluded from much of public life, are being asked to distance themselves even further, deepening their loneliness. Asian people are suffering racist insults, fueled by a president who insists on labeling the new coronavirus the Chinese virus. Incidents of domestic violence and child abuse are likely to spike as people are forced to stay in unsafe homes. Children, whose bodies are mostly spared by the virus, may endure mental trauma that stays with them into adulthood.

Read: The kids arent all right

After the pandemic, people who recover from COVID-19 might be shunned and stigmatized, as were survivors of Ebola, SARS, and HIV. Health-care workers will take time to heal: One to two years after SARS hit Toronto, people who dealt with the outbreak were still less productive and more likely to be experiencing burnout and post-traumatic stress. People who went through long bouts of quarantine will carry the scars of their experience. My colleagues in Wuhan note that some people there now refuse to leave their homes and have developed agoraphobia, says Steven Taylor of the University of British Columbia, who wrote The Psychology of Pandemics.

But there is also the potential for a much better world after we get through this trauma, says Richard Danzig of the Center for a New American Security. Already, communities are finding new ways of coming together, even as they must stay apart. Attitudes to health may also change for the better. The rise of HIV and AIDS completely changed sexual behavior among young people who were coming into sexual maturity at the height of the epidemic, Conis says. The use of condoms became normalized. Testing for STDs became mainstream. Similarly, washing your hands for 20 seconds, a habit that has historically been hard to enshrine even in hospitals, may be one of those behaviors that we become so accustomed to in the course of this outbreak that we dont think about them, Conis adds.

Pandemics can also catalyze social change. People, businesses, and institutions have been remarkably quick to adopt or call for practices that they might once have dragged their heels on, including working from home, conference-calling to accommodate people with disabilities, proper sick leave, and flexible child-care arrangements. This is the first time in my lifetime that Ive heard someone say, Oh, if youre sick, stay home, says Adia Benton, an anthropologist at Northwestern University. Perhaps the nation will learn that preparedness isnt just about masks, vaccines, and tests, but also about fair labor policies and a stable and equal health-care system. Perhaps it will appreciate that health-care workers and public-health specialists compose Americas social immune system, and that this system has been suppressed.

Aspects of Americas identity may need rethinking after COVID-19. Many of the countrys values have seemed to work against it during the pandemic. Its individualism, exceptionalism, and tendency to equate doing whatever you want with an act of resistance meant that when it came time to save lives and stay indoors, some people flocked to bars and clubs. Having internalized years of anti-terrorism messaging following 9/11, Americans resolved to not live in fear. But SARS-CoV-2 has no interest in their terror, only their cells.

Years of isolationist rhetoric had consequences too. Citizens who saw China as a distant, different place, where bats are edible and authoritarianism is acceptable, failed to consider that they would be next or that they wouldnt be ready. (Chinas response to this crisis had its own problems, but thats for another time.) People believed the rhetoric that containment would work, says Wendy Parmet, who studies law and public health at Northeastern University. We keep them out, and well be okay. When you have a body politic that buys into these ideas of isolationism and ethnonationalism, youre especially vulnerable when a pandemic hits.

Graeme Wood: The Chinese virus is a test. Dont fail it.

Veterans of past epidemics have long warned that American society is trapped in a cycle of panic and neglect. After every crisisanthrax, SARS, flu, Ebolaattention is paid and investments are made. But after short periods of peacetime, memories fade and budgets dwindle. This trend transcends red and blue administrations. When a new normal sets in, the abnormal once again becomes unimaginable. But there is reason to think that COVID-19 might be a disaster that leads to more radical and lasting change.

The other major epidemics of recent decades either barely affected the U.S. (SARS, MERS, Ebola), were milder than expected (H1N1 flu in 2009), or were mostly limited to specific groups of people (Zika, HIV). The COVID-19 pandemic, by contrast, is affecting everyone directly, changing the nature of their everyday life. That distinguishes it not only from other diseases, but also from the other systemic challenges of our time. When an administration prevaricates on climate change, the effects wont be felt for years, and even then will be hard to parse. Its different when a president says that everyone can get a test, and one day later, everyone cannot. Pandemics are democratizing experiences. People whose privilege and power would normally shield them from a crisis are facing quarantines, testing positive, and losing loved ones. Senators are falling sick. The consequences of defunding public-health agencies, losing expertise, and stretching hospitals are no longer manifesting as angry opinion pieces, but as faltering lungs.

After 9/11, the world focused on counterterrorism. After COVID-19, attention may shift to public health. Expect to see a spike in funding for virology and vaccinology, a surge in students applying to public-health programs, and more domestic production of medical supplies. Expect pandemics to top the agenda at the United Nations General Assembly. Anthony Fauci is now a household name. Regular people who think easily about what a policewoman or firefighter does finally get what an epidemiologist does, says Monica Schoch-Spana, a medical anthropologist at the Johns Hopkins Center for Health Security.

Such changes, in themselves, might protect the world from the next inevitable disease. The countries that had lived through SARS had a public consciousness about this that allowed them to leap into action, said Ron Klain, the former Ebola czar. The most commonly uttered sentence in America at the moment is, Ive never seen something like this before. That wasnt a sentence anyone in Hong Kong uttered. For the U.S., and for the world, its abundantly, viscerally clear what a pandemic can do.

The lessons that America draws from this experience are hard to predict, especially at a time when online algorithms and partisan broadcasters only serve news that aligns with their audiences preconceptions. Such dynamics will be pivotal in the coming months, says Ilan Goldenberg, a foreign-policy expert at the Center for a New American Security. The transitions after World War II or 9/11 were not about a bunch of new ideas, he says. The ideas are out there, but the debates will be more acute over the next few months because of the fluidity of the moment and willingness of the American public to accept big, massive changes.

One could easily conceive of a world in which most of the nation believes that America defeated COVID-19. Despite his many lapses, Trumps approval rating has surged. Imagine that he succeeds in diverting blame for the crisis to China, casting it as the villain and America as the resilient hero. During the second term of his presidency, the U.S. turns further inward and pulls out of NATO and other international alliances, builds actual and figurative walls, and disinvests in other nations. As Gen C grows up, foreign plagues replace communists and terrorists as the new generational threat.

One could also envisage a future in which America learns a different lesson. A communal spirit, ironically born through social distancing, causes people to turn outward, to neighbors both foreign and domestic. The election of November 2020 becomes a repudiation of America first politics. The nation pivots, as it did after World War II, from isolationism to international cooperation. Buoyed by steady investments and an influx of the brightest minds, the health-care workforce surges. Gen C kids write school essays about growing up to be epidemiologists. Public health becomes the centerpiece of foreign policy. The U.S. leads a new global partnership focused on solving challenges like pandemics and climate change.

In 2030, SARS-CoV-3 emerges from nowhere, and is brought to heel within a month.

Listen to Ed Yong discuss this story on an episode of Social Distance, The Atlantics podcast about living through a pandemic:

Subscribe to Social Distance on Apple Podcasts or Spotify (How to Listen)

Read more:
How the Pandemic Will End - The Atlantic

EAST HANOVER, N.J., March 28, 2020 /PRNewswire/ --Novartis today announced results from a prespecified analysis of pooled data from three Phase III studies evaluating the safety and efficacy of inclisiran, its first-in-class investigational treatment for hyperlipidemia in adults. The data was presented during a Late Breaker session at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC Virtual). The pooled analysis of the ORION-9, -10 and -11 Phase III trials showed a durable and potent reduction in LDL-C of 51% when used in addition to other lipid-lowering therapies (LLT) over 17 months of treatment1. The prespecified analysis of pooled data is consistent with the efficacy and safety findings of the individual Phase III trial results recently published in The New England Journal of Medicine.

Additionally, a prespecified exploratory analysis using the safety reporting from all three trials indicated fewer MACE with inclisiran compared to placebo (7.1%, 9.4% respectively)1. The overall safety and tolerability profile was generally similar between the inclisiran and placebo groups. While these preliminary observations are based on a low number of events, they are consistent with the general concept that however LDL-C is lowered, it is thought to result in reduced risk of future cardiovascular events2. This further supports the research currently underway in the Phase III ORION-4 trial. The ORION-4 trial aims to recruit 15,000 participants from 150 sites in the United States and the United Kingdom with pre-existing atherosclerotic cardiovascular disease (ASCVD) and who are unable to achieve LDL-C goal. Expected to finish in 2024, this trial will bring additional information on inclisiran's effects on cardiovascular outcomes.

"There remains a compelling need for new and novel LDL-C-lowering therapies given the residual risk faced by many patients with atherosclerotic cardiovascular disease and the inability of oral lipid-lowering therapy alone to achieve important LDL targets," said ORION-10 principal investigator R. Scott Wright, M.D., Professor of Medicine, Consultant in Cardiology, Mayo Clinic in Rochester, Minnesota. "Inclisiran harnesses the body's natural mechanisms for RNA silencing and lowers LDL-C. This analysis confirmed that twice-yearly dosing of inclisiran achieved durable and potent reductions in LDL-C in the phase III studies."

"After decades of declining cardiovascular disease mortality, it is on the rise again, renewing the urgency behind our longstanding commitment to and extensive experience in this space," said David Platt, M.D., Vice President, US Clinical Development and Medical Affairs, Cardiovascular, Renal & Metabolism Medical Unit, Novartis Pharmaceuticals. "We are excited by the results we have seen to date with inclisiran, and we look forward to the potential opportunity to make the first and only LDL-C-lowering treatment in the small interfering RNA (siRNA) class available to patients with ASCVD and familial hypercholesterolemia."

Inclisiran is currently under review by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for use in adults with ASCVD or heterozygous familial hypercholesterolemia (HeFH) who have elevated LDL-C while being on a maximum tolerated dose of a LLT. Inclisiran was administered subcutaneously with an initial dose, again at 3 months and then every 6 months, offering a unique dosing regimen. If approved, inclisiran will be the first and only LDL-C-lowering treatment in the siRNA class.

Hyperlipidemia refers to the high level of lipids (fats, cholesterol, triglycerides), such as LDL-C, found in the blood that are either acquired or from genetic disorders3. LDL-C is the most readily modifiable risk factor for ASCVD4-9. Despite the widespread use of therapies to reduce LDL-C, the majority of patients do not reach guideline-recommended treatment goals, leaving them at continued risk of a life-threatening condition10.

About the pooled analysisThe pooled analysis includes data from inclisiran's ORION-9, -10 and -11 trials, which are multicenter, double-blind, randomized, placebo-controlled,18-month studies evaluating inclisiran in patients with heterozygous familial hypercholesterolemia (ORION-9), ASCVD (ORION-10) and ASCVD or ASCVD risk equivalents (ORION-11). The primary endpoints for these studies were percentage change in LDL-C from baseline to 17 months and time-adjusted percentage change in LDL-C from baseline between 3 months and up to 18 months. The primary endpoints were achieved in all three studies. The prespecified analysis of pooled data assessed inclisiran's efficacy for lowering of LDL-C and other lipids/lipoproteins, as well as safety and tolerability, across these studies1.

In the prespecified analysis of pooled data, inclisiranresulted in placebo-adjusted LDL-C reduction at 17 months of 51% and a time-adjusted placebo-adjusted percentage reduction in LDL-C between 3 and 18 months of 51%. In a prespecified exploratory safety analysis, MACE were significantly lower with inclisiran versus placebo (7.1%, 9.4% respectively); measures included non-fatal myocardial infarction (5.2%, 7.8%), stroke (0.9%, 1.0%), cardiovascular death (0.9%, 0.8%) and resuscitated cardiac arrest (0.2%, 0.1%). The overall safety and tolerability profile was generally similar between inclisiran and placebo groups. No differences in adverse outcomes were observed between groups1.

About inclisiranInclisiran, an investigational cholesterol-lowering treatment, was added to the pipeline from the Novartis acquisition of The Medicines Company. Inclisiran will potentially be the first and only LDL-C lowering siRNA treatment. It is intended to be administered by a healthcare professional by subcutaneous injection with an initial dose, again at 3 months and then every 6 months thereafter. Its twice-yearly dosing by subcutaneous injection may integrate seamlessly into a patient's healthcare routine. As a siRNA, inclisiran is thought to harness the body's natural process of clearing LDL-C from the bloodstream. Inclisiran is a double-stranded siRNA, conjugated on the sense strand with triantennary N-acetylgalactosamine (GalNAc) to facilitate uptake by hepatocytes. In hepatocytes, inclisiran increases LDL-C receptor recycling and expression on the hepatocyte cell surface, thereby increasing LDL-C uptake by hepatocytes and lowering LDL-C levels in the circulation. Data from each of the Phase III studies was recently published online, ahead of print, in The New England Journal of Medicine11,12. A cardiovascular outcomes trial, ORION-4, is ongoing.

In the Phase III studies, inclisiran was reported to be well-tolerated with a safety profile similar to placebo. The most common adverse reactions reported (3% of patients treated with inclisiran and occurring more frequently than placebo) were, diabetes mellitus, hypertension, nasopharyngitis, arthralgia, back pain, dyspnea, bronchitis and upper respiratory tract infection. Adverse events at the injection site were more frequent with inclisiran than placebo and were generally mild and none were severe or persistent11,12.

Novartis has obtained global rights to develop, manufacture and commercialize inclisiran under a license and collaboration agreement with Alnylam Pharmaceuticals.

About Novartis in Cardiovascular-Renal-MetabolismBending the curve of life requires addressing some of society's biggest public health concerns. Novartis has an established and expanding presence in diseases covering the heart, kidney and metabolic system. In addition to essential treatment Entresto (sacubitril/valsartan), Novartis has a growing pipeline of potentially first-in-class molecules addressing cardiovascular, metabolic and renal diseases.

DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "may," "could," "would," "expect," "anticipate," "seek," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About NovartisLocated in East Hanover, NJ Novartis Pharmaceuticals Corporation an affiliate of Novartis is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis employs about 15,000 people in the United States. For more information, please visit http://www.novartis.us.

Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartisnews For Novartis multimedia content, please visit http://www.novartis.com/news/media-libraryFor questions about the site or required registration, please contact media.relations@novartis.com

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Among the headlines from yesterdays meetings of the newly-empowered government and the national security council, one that caught the eye was the announcement of a cat diagnosed with coronavirus caught from its owner.

The cat was reported to have caught the virus from close contact with its owner, who had recently returned from Italy. When the cat became ill, its stool was examined and traces of the virus discovered.

The experts were quick to reassure pet owners that the case was exceptional, that animals were not considered a vector for the disease, and that there was no reason to be afraid either for their pets or for themselves.

But one animal virologist has raised questions about the whole story.

Hans Nauwynck is a professor at the faculty of veterinary medicine at the University of Ghent, and a specialist in virology. The news of the corona cat took him by surprise.

Before sending this news out into the world, I would have had some other tests carried out, he told Het Laatste Nieuws. When you hear about this right now, I wouldnt wish to be a cat tomorrow.

The discovery was made by the vet faculty at Liege university, who concluded the infection passed from human to cat and not the other way around.

Look, I have no criticism of my colleagues at Liege university, he stressed. The diagnosis has been made, Ive no doubt about the result, but were dealing here with a PCR test, a way of identifying genetic material of the virus.

The polymerase chain reaction (PCR) test allows scientists to multiply a very small sample of genetic material to produce a quantity large enough to study.

Im simply questioning the interpretation of the results. The test is positive for corona, fine, but how was the test carried out? How was the sample taken, and can that result be trusted? I would advise people to slow down. There may somehow have been genetic material from the owner in the sample, and so the sample is contaminated.

To be absolutely certain, he said, more tests should have been done to confirm the initial result, and certainly before making an announcement to the world.

I think its too bad they didnt look further, he said. There should also have been research carried out to see if the cat had produced antibodies. Im worried that people will be scared by this news and animals will be the ones to suffer, and thats not right. As scientists we ought to put out clear and full information, and I dont think that has happened.

In the latest update, the cat is doing well. Its owner is also recovering, albeit more slowly.

Alan HopeThe Brussels Times

Read more from the original source:
The curious case of the cat with corona - The Brussels Times

At least eight strains of the coronavirus are making their way around the globe, creating a trail of death and disease that scientists are tracking by their genetic footprints.

While much is unknown, hidden in the virus'unique microscopic fragments are clues to the origins of its original strain, how it behaves as it mutates and which strains are turning into conflagrations while others are dying out thanks to quarantine measures.

KATHRYN GEORGE/STUFF

Scientists are tracking eight strains of the coronavirus by their genetic footprints.

Huddled in once bustling and now almost empty labs, researchers who oversaw dozens of projects are instead focused on one goal: tracking the current strains of the SARS-CoV-2 virus that cause the illness Covid-19.

Labs around the world are turning their sequencing machines, most about the size of a desktop printer, to the task of rapidly sequencing the genomes of virus samples taken from people sick with Covid-19. The information is uploaded to a website called NextStrain.org that shows how the virus is migrating and splitting into similar but new subtypes.

READ MORE:* Three months into the pandemic, here is what we know about the coronavirus* Coronavirus isn't alive and that's why it's so hard to kill* Coronavirus vaccine hunters: meet the scientists racing to find a cure* Key terms of the coronavirus outbreak, explained: From asymptomatic to zoonotic

While researchers caution they're only seeing the tip of the iceberg, the tiny differences between the virus strains suggest shelter-in-place orders are working in some areas and that no one strain of the virus is more deadly than another. They also say it does not appear the strains will grow more lethal as they evolve.

"The virus mutates so slowly that the virus strains are fundamentally very similar to each other," said Charles Chiu, a professor of medicine and infectious disease at the University of California, San Francisco School of Medicine.

The SARS-CoV-2 virus first began causing illness in China sometime between mid-November and mid-December. Its genome is made up of about 30,000 base pairs. Humans, by comparison, have more than 3 billion. So far even in the virus's most divergent strains scientists have found only 11 base pair changes.

That makes it easy to spot new lineages as they evolve, said Chiu.

"The outbreaks are trackable. We have the ability to do genomic sequencing almost in real-time to see what strains or lineages are circulating," he said.

So far, most cases on the USWest Coast are linked to a strain first identified in Washington state. It may have come from a man who had been in Wuhan, China, the virus' epicentre, and returned home on January 15. It is only three mutations away from the original Wuhan strain, according to work done early in the outbreak by Trevor Bedford, a computational biologist at Fred Hutch, a medical research centrein Seattle.

On the East Coast there are several strains, including the one from Washington and others that appear to have made their way from China to Europe and then to New York and beyond, Chiu said.

BEWARE PRETTY PHYLOGENETIC TREES

This isn't the first time scientists have scrambled to do genetic analysis of a virus in the midst of an epidemic. They did it with Ebola, Zika and West Nile, but nobody outside the scientific community paid much attention.

"This is the first time phylogenetic trees have been all over Twitter," said Kristian Andersen, a professor at Scripps Research, a nonprofit biomedical science research facility in La Jolla, California, speaking of the diagrams that show the evolutionary relationships between different strains of an organism.

The maps are available on NextStrain, an online resource for scientists that uses data from academic, independent and government laboratories all over the world to visually track the genomics of the SARS-CoV-2 virus. It currently represents genetic sequences of strains from 36 countries on six continents.

While the maps are fun, they can also be "little dangerous" said Andersen. The trees showing the evolution of the virus are complex and it's difficult even for experts to draw conclusions from them.

"Remember, we're seeing a very small glimpse into the much larger pandemic. We have half a million described cases right now but maybe 1000 genomes sequenced. So there are a lot of lineages we're missing," he said.

MANU FERNANDEZ/AP

Health workers applaud in support of the medical staff that are working on the Covid-19 virus outbreak in Spain.

DIFFERENT SYMPTOMS, SAME STRAINS

Covid-19 hits people differently, with some feeling only slightly under the weather for a day, others flat on their backs sick for two weeks and about 15 per centhospitalised. Currently, an estimated 1 per centof those infected die. The rate varies greatly by country and experts say it is likely tied to testing rates rather than actual mortality.

Chiu says it appears unlikely the differences are related to people being infected with different strains of the virus.

"The current virus strains are still fundamentally very similar to each other," he said.

The Covid-19 virus does not mutate very fast. It does so eight to 10 times more slowly than the influenza virus, said Anderson, making its evolution rate similar to other coronaviruses such as Ebola, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).

It's also not expected to spontaneously evolve into a form more deadly than it already is to humans. The SARS-CoV-2 is so good at transmitting itself between human hosts, said Andersen, it is under no evolutionary pressure to evolve.

GETTY IMAGES

The Covid-19 virus does not mutate very fast. It does so eight to 10 times more slowly than the influenza virus.

SHELTER IN PLACE WORKING IN CALIFORNIA

Chiu's analysis shows California's strict shelter in place efforts appear to be working.

Over half of the 50 SARS-CoV-2 virus genomes his San Francisco-based lab sequenced in the past two weeks are associated with travel from outside the state. Another 30 per centare associated with health care workers and families of people who have the virus.

"Only 20 per centare coming from within the community. It's not circulating widely," he said.

That's fantastic news, he said, indicating the virus has not been able to gain a serious foothold because of social distancing.

It's like a wildfire, Chiu said. A few sparks might fly off the fire and land in the grass and start new fires. But if the main fire is doused and its embers stomped out, you can kill off an entire strain. In California, Chiu sees a lot of sparks hitting the ground, most coming from Washington, but they're quickly being put out.

An example was a small cluster of cases in Solano County, northeast of San Francisco. Chiu's team did a genetic analysis of the virus that infected patients there and found it was most closely related to a strain from China.

At the same time, his lab was sequencing a small cluster of cases in the city of Santa Clara in Silicon Valley. They discovered the patients there had the same strain as those in Solano County. Chiu believes someone in that cluster had contact with a traveller who recently returned from Asia.

"This is probably an example of a spark that began in Santa Clara, may have gone to Solano County but then was halted," he said.

The virus, he said, can be stopped.

CHINA IS AN UNKNOWN

So far researchers don't have a lot of information about the genomics of the virus inside China beyond the fact that it first appeared in the city of Wuhan sometime between mid-November and mid-December.

The virus's initial sequence was published on January 10 by professor Yong-Zhen Zhang at the Shanghai Public Health Clinical Center. But Chiu says scientists don't know if there was just one strain circulating in China or more.

"It may be that they haven't sequenced many cases or it may be for political reasons they haven't been made available," said Chiu. "It's difficult to interpret the data because we're missing all these early strains."

Researchers in the United Kingdom who sequenced the genomes of viruses found in travellers from Guangdong in south China found those patients' strains spanned the gamut of strains circulating worldwide.

"That could mean several of the strains we're seeing outside of China first evolved there from the original strain, or that there are multiple lines of infection. It's very hard to know," said Chiu.

THE VIRUS DID NOT COME FROM A LAB

While there remain many questions about the trajectory of the Covid-19 disease outbreak, one thing is broadly accepted in the scientific community: The virus was not created in a lab but naturally evolved in an animal host.

SARS-CoV-2's genomic molecular structure - think the backbone of the virus - is closest to a coronavirus found in bats. Parts of its structure also resemble a virus found in scaly anteaters, according to a paper published earlier this month in the journal Nature Medicine.

Someone manufacturing a virus targeting people would have started with one that attacked humans, wrote National Institutes of Health Director Francis Collins in an editorial that accompanied the paper.

Andersen was lead author on the paper. He said it could have been a one-time occurrence.

"It's possible it was a single event, from a single animal to a single human," and spread from there.

- USA Today

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Eight strains of the coronavirus are circling the globe. They're giving scientists clues - Stuff.co.nz

Some viruses look like moon landers.

Called phages, they hijack bacteria by landing on the hapless cells and injecting them with a ream of genetic material. Then, the phages use the commandeered cells to multiply.

Similar to the new coronavirus, these phages are excellent parasites. They can be aggressive, dogged, and seem to act with purpose. Yet, many microbiologists who know viruses best say it's a stretch to call any virus truly alive. And so, they can't be killed only disarmed, like pulling the plug on an appliance.

But today, with a rapidly spreading viral pandemic that's stirring serious unease in American emergency rooms, it doesn't really matter if a virus meets biologists' definitions of dead or alive. Whatever these entities are, they're powerful.

"It's more of a philosophical question," said Ryan Relich, a medical microbiologist at Indiana University's School of Medicine, of whether viruses are alive or not.

"What's more important is that they're winning," he said.

Today, the coronavirus isn't just winning. It's dominating us. It's closed our arenas. Shut down our bars. Emptied California beaches. The increasingly austere governor of New York is now demanding ventilators from the federal government. Our best, and most critical, defense until a vaccine is developed in a year at the earliest is social distancing: We're avoiding infected persons and hiding from the microbes themselves, which are basically genes surrounded by a shell.

Viruses, like coronavirus, have become globally dominant because they evolved to become master replicators. But they can't multiply alone, so they take over other cells and exploit this cellular machinery to multiply. It's exquisite parasitism. A single coronavirus-infected cell can manufacture millions of coronaviruses.

"Parasitism is an old, venerated way of making a living," said Siobain Duffy, who researches the evolution of viruses at Rutgers University.

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Now, lets get it out of the way: viruses are not alive. They do not possess all the characteristics of a living organisms so, no, you cannot kill them. You can, however, inactivate them, denature them, neutralize them, etc. pic.twitter.com/ODGVoa5q1J

Efra Rivera-Serrano, PhD (@NakedCapsid) March 17, 2020

A colorized image of a cell (brown) from a patient infected with coronavirus (pink).

Yet, unlike parasites such as intestinal worms, viruses are almost completely dependent upon the cells they hijack. "Viruses don't actually do anything on their own," explained Relich.

They don't breathe. They don't eat. They don't make energy. They appear mindless, floating around with the possibility of landing on a cell. "They don't get up and go to work every day," said Relich. "I dont consider them to be living. But hey, maybe you want to consider them to be alive so that its easier to personify them or rationalize things in a more palatable way."

So, microbiologists can make a good argument that viruses don't have the same hallmarks of living as do amoebas, elephants, and emus.

But maybe viruses are alive just in another sense of alive. After all, life has been evolving on Earth for some 3.8 billion years, noted Duffy. There are all kinds of curious things out there that might blur the boundary between alive and not alive. For example, there are viruses with longer genomes than bacteria (which we all agree are alive), and viruses that make some bacteria better at things, like photosynthesis. Our human DNA is embedded with some viral genetic material, too, noted Relich.

"Life continues to astound us."

"People want a clear dividing line between life and non-life," said Duffy. But that line might be blurrier than we think, she added.

The quandary of whether a virus can ever be killed, then, is a bottomless philosophical hole that may never have a certain answer. But it's safe to say, at least, that there are effective ways "to inactivate viruses or otherwise render them kaput," said Relich.

Chemicals like bleach and rubbing alcohols can massively damage the exterior wrappings of viruses, which for some include a fatty membrane envelope, making viruses useless. Thorough hand washing destroys these viral shells, too. Though there are no proven antiviral medications for coronavirus (and there may not be for many months), these types of drugs are designed to disrupt a virus' activity. For instance, the HIV drug Enfuvirtide blocks the virus from even attaching to human cells. Other drugs stop viruses from replicating, once they've already slipped inside a cell.

There's another very certain thing about viruses. Humanity has a ton to learn about them. There are countless species, and they're everywhere. "There are more viruses in this world than there are cells," said Duffy. But only 6,828 virus species have been formally named by scientists. Meanwhile, there could be millions more species out there. Finding and understanding theses microscopic entities could reveal much more about their nature, and "lives."

"We need more research, we need more researchers, we need more funding for research," said Relich.

Only in 1977 did humanity discover the third domain of life, a massive, ancient group of organisms called archaea (the other two domains are bacteria and eukaryotes which include humans.) What might the great diversity of viruses in this domain, still being discovered, tell us?

"Life continues to astound us," said Duffy. Indeed.

For now, we're focused on the minority of viruses that can threaten our ability to breathe, like the new coronavirus which can result in the serious respiratory disease COVID-19. And for good reason.

"It's to our own advantage to know our enemies as well as possible," said Relich.

Even if they can't be killed.

"Whether or not theyre alive, viruses influence life," said Duffy.

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You can't kill the coronavirus. That's OK. - Mashable SE Asia

From left, College of Medicine graduate student Jamie Johnston, College of Medicine Associate Professor Jose Pinto, College of Medicine graduate student Maicon Landim-Vieira and Department of Biological Science Professor P. Bryant Chase.Photo courtesy of P. Bryant Chase.

Florida State University researchers working in an international collaboration have identified new genetic variants that cause heart disease in infants, and their research has led to novel insights into the role of a protein that affects how the heart pumps blood. It is a discovery that could lead to new treatments for people suffering from heart disease.

In two separate papers, Jose Pinto, an associate professor in the College of Medicine, and P. Bryant Chase, a professor in the Department of Biological Science, worked with doctoral students Jamie Johnston and Maicon Landim-Vieira to explore a disease that caused the heart to pump with too little force. Their work was published in the Journal of Biological Chemistry and in Frontiers in Physiology.

The researchers discovered new interactions within parts of a protein called troponin. Troponin has three parts troponin C, troponin I and troponin T that work together to regulate the hearts pumping of blood. The FSU researchers uncovered interactions of troponin C with portions of troponin T that can decrease the force of the heartbeat, something scientists had not previously noticed.

All of these proteins, they work like an orchestra, Pinto said. What is the main thing for an orchestra? To be in harmony, in balance. You need to have a good balance and you need to be in harmony, otherwise you will not produce good music. If one of these proteins is not in sync with the other proteins, you will not have your orchestra in harmony or balanced well, and then that will lead to the disease.

Most previous work had focused on interactions between troponin C and troponin I, or between troponin T and another protein called tropomyosin. The new interaction between troponin C and troponin T is an interaction that will modulate how much force the heart generates in each heartbeat, Pinto said. If you increase the number of these interactions, most likely you decrease contraction of the heart, and if you prevent these interactions, very likely you increase the force of contraction in each heartbeat.

But science sometimes leads to more questions than answers. A related study by the same FSU researchers reported a new combination of genetic variants in a different part of troponin C that also caused heart disease in infants. Rather than uncovering new interactions among the parts of troponin, this study led researchers to conclude that there must be an unknown role for troponin, possibly in the cell nucleus, Chase said.

In that research, DNA sequencing showed that a mother and a father had different variants that both affected the troponin C protein. Although their cell function was altered in such a way that researchers expected them to have heart problems, they did not show signs of heart disease. Their children, however, had both variants, and though their cell functioning appeared to be more normal, they developed deadly heart disease.

Some experiments provide a lot of immediate insight, but other times we find out that we just dont understand everything that we think we do, Chase said. As much as weve learned, as much as we do understand, theres a lot more thats unknown. And its those times that can eventually lead to brand new, unexpected insights.

Understanding the interactions between the parts of the troponin protein and also troponins various roles in heart cells will help guide new treatments for heart disease, both for the disease caused by the specific genetic variants the researchers discovered and for heart disease in general.

These diseases are caused by seemingly small changes in the DNA, Chase said. There are genetic technologies to reverse that, to introduce the common DNA sequence, but applications of genetic technologies to human disease are in their infancy and theres not a surefire and ethical way to apply changes in the genome to all the heart patients who could benefit from it. Im sure there will be ways to correct genetic variants for a number of diseases, but the medical community is only just beginning to find out how to do that safely for people.

Researchers from the FSU Translational Science Laboratory, Federal University of Rio de Janeiro, Federal University of Minas Gerais, Tel Aviv Sourasky Medical Center, Tel Aviv University and Yale University contributed to this work. The research was supported by the American Heart Association and the National Institutes of Health.

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FSU researchers help discover new genetic variants that cause heart disease in infants - Florida State News

"Access to testing is really the major tool we have right now to fight this new coronavirus," says Dr. Keith Jerome, who runs a University of Washington lab in Seattle that can now test for the virus. Jonathan Hamilton/NPR hide caption

"Access to testing is really the major tool we have right now to fight this new coronavirus," says Dr. Keith Jerome, who runs a University of Washington lab in Seattle that can now test for the virus.

It's been a busy week at the virology lab run by UW Medicine, which includes the University of Washington's medical school and hospitals.

"We've already gone to three shifts," says Dr. Keith Jerome, a professor in the department of laboratory medicine who runs the lab. "People are going to be here basically all the time."

The lab is processing about 100 coronavirus tests a day. But it's prepared to do more than 1,000 a day immediately and could quickly increase that to 4,000, Jerome says.

The demand for tests is rising. Seattle is at the center of a coronavirus outbreak that has already claimed the lives of 10 people in Washington state.

One reason the lab is ready to test lots of people is its state-of-the-art equipment, including twin devices that extract genetic material from specimens.

"That all happens robotically," Jerome says, as he gives me a tour of the lab's testing area. "You can see the arms here moving back and forth. This robot is working on 96 specimens at a time. We have two of them. This is part of the magic of moving so many specimens through this laboratory."

In another area of the lab is a room full of instruments that take bits of genetic material from a virus and make millions of copies. That's critical for detecting an infection, Jerome says.

"Right now this is our limiting factor," he says, adding that they've already asked to borrow more of the instruments from other labs affiliated with the university.

But the lab's readiness also is the result of months of planning.

Jerome and other virologists started the process in January, after hearing reports about the coronavirus outbreak in China.

"Our opinion was, this is probably not going to be a problem, this is probably going to be a waste of our effort and some money, but we owe it to the people of our area to be prepared," he says.

So the scientists developed an assay and began using it test specimens sent in for research purposes.

At first, the tests found no infections, says Dr. Alex Greninger, the lab's assistant director. Then, on Feb. 28, one came back positive.

"That was on Friday at 4 p.m.," he says. "And then Saturday morning the FDA came out with a new regulation that allowed us to perform testing."

The change at the Food and Drug Administration was a new policy that allowed sophisticated labs like the one at UW Medicine to develop and use their own coronavirus tests before the agency had reviewed them.

On Monday and Tuesday, the lab quietly began accepting specimens for clinical use and preparing for high-volume testing.

"It was intense," Greninger says, adding that he and colleagues were working past midnight to make sure the system functioned properly.

But the hard part wasn't the testing itself, Greninger says, but the logistics.

For example, "how many swabs you're going to take from each patient, how you're going to handle sending results and samples to the state public health lab," he says.

Then on Wednesday, Jerome and Greninger held a press conference to announce that the lab was officially open for business.

Now they are expecting an avalanche of specimens. And that's a good thing, Jerome says.

"Access to testing is really the major tool we have right now to fight this new coronavirus," he says

Even with the lab's increased capacity, though, testing remains limited to people who have symptoms including fever and a dry cough.

"My goal is everyone who needs a test can get one," Jerome says. "And that might be different than everyone who wants a test."

Local doctors say the lab will make a huge difference.

"It's a game changer," says Dr. Seth Cohen, medical director for infection prevention at UW Medical Center Northwest. "Previously when we would send those tests to the [Centers for Disease Control and Prevention] in Atlanta it was taking three to five days to get those tests back."

Now results often come back the same day. And that means doctors and hospitals can focus resources on the patients who are truly infected.

Conserving scarce resources will become critical if the coronavirus continues to spread, Cohen says.

"We did not plan on being at the epicenter of one of the outbreaks in the United States," Cohen says. "And we are preparing for the worst."

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Coronavirus Tests: Lab At University Of Washington Was Ready : Shots - Health News - NPR