A nurse administers a test at a drive-through COVID-19 coronavirus testing station, set up by the University of Washington Medical Center in Seattle. Ted S. Warren/AP hide caption
A nurse administers a test at a drive-through COVID-19 coronavirus testing station, set up by the University of Washington Medical Center in Seattle.
The other night, I had a patient in the ER where I work come in with fever, cough and shortness of breath. It would have been a routine visit, if not for the novel coronavirus currently sweeping the globe. The patient was concerned about the virus, and so were we. She had recently traveled to a conference in a country with known cases of COVID-19, as the disease caused by the coronavirus is called. She was middle-aged and had HIV, which we worried could increase her risk of serious illness from the virus. We contacted the department of health, where all testing in my state is currently performed, to request permission to test for the coronavirus.
The verdict? Denied.
Since the patient did not require hospital resources, like an oxygen mask or IV fluids, we discharged her home, urging her to self-quarantine and return if her symptoms worsened.
Every ER doctor that I work with already has several stories like this. This week, in Massachusetts, testing has been permitted only for patients with respiratory symptoms requiring hospitalization, or for patients with such symptoms who have traveled to endemic areas or had contact with confirmed coronavirus cases. Similar criteria apply in other states. The problem with this approach is that, according to all indicators, it is almost certainly missing a large number of cases.
Strong evidence suggests that the coronavirus is already spreading within the community and has been for weeks. After the first confirmed case appeared in the United States on Jan. 20, scientists in Seattle who had been collecting swabs to study influenza went rogue and, against the directive of the Food and Drug Administration and Centers for Disease Control and Prevention, developed a test and began looking for coronavirus in their flu samples. In late February, they quickly found their first positive a teenager with no recent travel and no sick contacts. Genetic sequencing of the virus by the same researchers suggested that the virus had likely been circulating in the community for as long as six weeks.
Now cases with no recent travel and no known contacts are emerging everywhere. Earlier this week, public health experts from Johns Hopkins confirmed that the virus is likely spreading undetected in the community. Put another way, this thing is probably out of the barn.
If that's the case, then why are we still facing such strict limitations on who we can test? There isn't a clear answer, but it seems to be a function of a woefully inadequate supply of test kits. In other words, what few tests we do have are being rationed for the people who need them most, like those requiring hospital admission. While South Korea has run nearly 250,000 tests and has capacity to test 10,000 people per day, current estimates suggest the United States has performed only about 19,000 tests. Here's another way to express just how far behind we are in terms of testing as of March 11, the United States had performed only 23 tests per million people, while the U.K had performed 347 per million, Italy 826 per million, and South Korea 3,692 per million, according to an analysis by multiple media outlets and the COVID Tracking Project.
Ashish Jha, director of the Harvard Global Health Institute, told NPR on Thursday that the United States' response has been "much, much worse than almost any other country that's been affected." He reached for words like "stunning," "fiasco" and "mind-blowing" to describe the situation.
This leads to a second, much more important question how were we so staggeringly unprepared to test for this virus? A number of hiccups have contributed. First, many test kits released by the CDC on Feb. 4 were defective. Designing and manufacturing these tests is challenging, and sometimes problems arise. There have been reports that early Chinese tests may have had a false negative rate as high as 50%. But rather than encourage university labs and private companies to help with test development, the FDA withheld permission for such work until Feb. 29. Contrast this with the response in South Korea, where a private biotechnology company began developing a test on Jan. 16, had a working version ready by Feb. 5t and had government approval for use one week later. That company is manufacturing enough kits to test a million people per week.
Private companies and academic labs are now developing their own tests. The Cleveland Clinic recently announced it had developed a rapid test for the virus. But concerns are mounting about a shortage of critical materials needed to run these tests.
The total failure to ensure that adequate testing would be available will likely prove to be the single most important factor in why the United States has been unable to contain the outbreak. As previously reported by NPR, Hong Kong, Singapore and South Korea all deployed an aggressive testing strategy very early on. This allowed them to find the first few cases and isolate them, preventing unchecked community spread. Because our government and public health authorities were unprepared, we have missed that precious opportunity in the United States, and it is going to cost people their lives.
This failure represents a profound abdication, at the highest levels of government, of responsibility to the health and security of the American population generally and of more vulnerable populations especially. Public health experts have known of the exceptional risk posed by novel coronaviruses for more than 20 years, but the current administration limited funding to the CDC and disbanded a White House unit expressly dedicated to preparing for a pandemic just like this one. Public statements from the top echelons of our government false comparisons to seasonal influenza, wildly misleading promises about access to testing, reassurances that everything is "perfect" continue to seed confusion and erode trust.
The most stunning illustration of this radical failure of leadership and responsibility occurred, for me, Thursday morning on C-SPAN. CDC Director Robert Redfield was testifying in front of Congress, and Rep. Debbie Wasserman Schultz was asking who was responsible for ensuring that those who needed to be tested could be tested. After several attempts to dodge the question, Redfield fell silent. He had no answer. He stared down at his desk, before slowly turning to a man seated next to him. It was Anthony Fauci, director of infectious diseases at the NIH. He had the courage to say what Redfield wouldn't.
"The system is not geared to what we need right now," he said. "And that is a failing."
What do we do now? We should still emphasize scaling up testing capacity in a massive way. Knowing exactly who has the disease will enable more effective quarantines, protect vulnerable populations and mitigate community spread. But the most critical measures occur at the individual level. Everyone should practice social distancing. That means curtailing all social interaction, canceling organized gatherings, working remotely, switching elbow bumps for handshakes and keeping a distance of several feet from others whenever possible. Everyone should also practice obsessive hand hygiene. That means washing your hands with soap and water for 20 seconds on a regular basis, and every time you come into contact with high-traffic areas, like a doorknob or subway pole. Avoid touching your face for any reason use a tissue to scratch an itch.
If you have any cold or flu-like symptoms, like fever, sore throat, cough, or muscle aches, you should wear a mask if you have access to one, isolate yourself, keep washing your hands and avoid contact with others as much as possible until at least two to three days after your symptoms have resolved. If you develop difficulty breathing, chest pain, profound weakness or confusion, then it's time to seek medical attention.
Community spread in the United States is already occurring, and the virus will likely reach a large number of people. But this is not the nightmare scenario. The nightmare scenario occurs if lots of people get sick at the same time. This could lead to a massive surge of ill patients arriving at hospitals all at once, which could easily overwhelm resources like oxygen tanks, ventilators and intensive care unit beds. If this happens, then people will die who otherwise might have recovered. Some European countries are already facing a situation like this. It is imperative that we spread out infections over time, or flatten the curve. This way hospitals will have adequate resources to treat everyone, and won't become overwhelmed. How do we flatten the curve? All of the individual actions I described above.
We're all in this together. If everyone does their part in limiting further spread, lives will be saved.
Clayton Dalton is a resident physician at Massachusetts General Hospital in Boston.
What if youre not in public health, but are thinking about your own personal chances and what your behavior should be?
If you imagine youve got a reproduction number of two, each persons infecting two others, on average. But some situations are more likely to spread infection than others. Weve found for things like Covid-19, its close-knit interactions that seem to be most important.
What we need to think about and what a lot of our modeling is certainly thinking about is not just how much transmission is happening, but where is that transmission happening. If youre going to change your behavior, think how to reduce those risky situations as much as possible.
If you were the average person, what would you pay attention to in terms of the news and the numbers?
One signal to watch out for is if the first case in an area is a death or a severe case, because that suggests you had a lot of community transmission already. As a back of the envelope calculation, suppose the fatality rate for cases is about 1 percent, which is plausible. If youve got a death, then that person probably became ill about three weeks ago. That means you probably had about 100 cases three weeks ago, in reality. In that subsequent three weeks, that number could well have doubled, then doubled, then doubled again. So youre currently looking at 500 cases, maybe a thousand cases.
I think the other thing that people do need to pay attention to is the risk of severe disease and fatality, particularly in older groups, in the over-70s, over-80s. Over all were seeing maybe 1 percent of symptomatic cases are fatal across all ages. Theres still some uncertainty on that, but whats also important is that 1 percent isnt evenly distributed. In younger groups, were talking perhaps 0.1 percent, which means that when you get into the older groups, youre potentially talking about 5 percent, 10 percent of cases being fatal.
In thinking about social behavior and thinking about your interactions, the question should be, How do we stop transmission getting into those groups where the impact could be really severe?
Hotels have always been in the business of providing a good nights rest, but a growing number of brands are adding tools to help guests chill out and get to sleep.
And that was before the anxiety caused by the coronavirus.
Well-being is top of mind for everyone today, and we think thats going to continue in the future, said Mia Kyricos, senior vice president and global head of well-being at Hyatt Hotels. If you think about the world we live in now, its 24/7. We increasingly have demands in work and life.
Starting April 1, Hyatt is rolling out a partnership with the Headspace meditation app. Guests will be able to get content on relaxation and sleep-guided meditation through the Hyatt loyalty program mobile app. The chain will also offer content from Headspace via TVs at its hotels.
Were starting with 200 properties and rolling out from there, growing globally, Ms. Kyricos said. Theres a real interest for people to practice self-care.
Data from the National Institutes of Health bears this out. A survey found that the number of American adults who reported meditating in the previous year tripled from 2012 to 2017, jumping to 14 percent from roughly 4 percent.
The wellness offerings may also provide an opportunity for hotels to increase revenue, according to a study released in December by CBRE, a commercial real estate services and investment firm. With a glut of new rooms projected to cut into hotels profits, owners and managers were looking for alternatives to raising room rates even before Covid-19 curbed travel and dampened demand. A CBRE analysis of 159 hotels with on-site spas found that, in 2018, spa revenue rose at a higher rate than overall operating revenue.
Spas have really expanded beyond the four walls, said Jenna Finkelstein, a director at CBRE who focuses on the hotel industry. More and more, wellness is becoming a major decision factor when choosing a hotel.
Last fall, Calm, an app that delivers meditation and nature sounds, announced a partnership with Novotel, one of the brands of the French hotel conglomerate Accor, to give guests guided meditations for relaxation and sleep. Starting this year, in a phased rollout, guests at Novotel hotels around the world may sign up for a free two-month subscription to Calms premium tier of content.
Big brands in many industries, but specifically in travel, are listening to their customers and realizing that wellness is more important to them, said Alex Will, chief strategy officer at Calm.
I think people are just searching for help with sleep and relaxation in general, Mr. Will said. Its just tiring. We have this always-on lifestyle now. It just creates a huge amount of stress and strain on the body.
Travel is becoming increasingly more stressful, Mr. Will said.
The growing awareness that sleep is an important part of staying healthy has increased the interest in technology that can help people fall and stay asleep.
Broadly speaking, travel and sleep are major-use cases above and beyond our partnership with Novotel, Mr. Will added. The thing we hear a lot from our users is if you cant sleep, it makes everything else feel very hard in day-to-day life.
Although these initiatives predate the coronavirus pandemic, they are well-positioned to address travelers current fears, said Ms. Finkelstein of CBRE.
Especially with coronavirus and everything thats happening, you are starting to see people either pull back on travel or be a little more cautious when they travel, she said.
In-room relaxation offerings, she added, were particularly well-suited to dealing with the worries of fearful guests. Anything you can do to limit contact with other people but still have some sort of experience related to wellness is especially good in the immediate climate, Ms. Finkelstein said. Providing that safe space for relaxation thats one immediate way to solve some of these travel-related anxieties.
Ms. Finkelstein characterized the trend as an offshoot of the digitally enhanced in-room fitness offerings a number of hotel brands have started in recent years and connected it to the rising interest in wellness and self-care. A lot of these fitness brands have almost a cult following, if you will, she said. When people are traveling, what they dont want is for their routine to get disrupted.
Amenities promoting sleep also are an extension of the hotel industrys arms race in bedding goods like mattresses and pillows, said Phil Cordell, senior vice president of new brand development for Hilton Hotels & Resorts. The availability of meditation and sleep guides is the next logical step, he said. Its an extension-slash-evolution of how some of the thinking has been over the past few years.
Hilton is starting a new brand called Tempo that will offer in-room relaxation and sleep content via TV as well as printed literature when its hotels open starting next year. (Construction began earlier this month on the first one in Louisville, Ky.)
Mr. Cordell said that improving sleep hygiene was a major goal for the Tempo brand. We have a million demands on our time when we travel, he said. Its hard for us to disconnect the brain sometimes. Sleep shortfall is one of the biggest challenges we face today.
As the coronavirus continues to spread across the globe, the news is coming at a fast and furious pace. But dont let the volume send you into a panic about your health and that of your loved ones.
The mantra is, Keep calm and carry on, said Dr. Marguerite Neill, an infectious disease expert at Brown University.
Heres a list of frequently asked questions about the coronavirus outbreak and its symptoms.
Common symptoms of this infection include fever, a dry cough, fatigue and difficulty breathing or shortness of breath. The illness causes lung lesions and pneumonia. Some of these symptoms overlap with those of the flu, making detection difficult, but runny noses and stuffy sinuses are less common.
Patients may also exhibit gastrointestinal problems or diarrhea, and Dr. Neill said we are learning about different symptoms as we go. Most people fall ill five to seven days after exposure, but symptoms may appear in as few as two days or as many as 14 days.
In some cases, people who had appeared stable rapidly deteriorate in the second week; anyone infected needs careful monitoring.
If you think youre sick as a result of the novel coronavirus, you can help safeguard your loved ones and community by staying at home, except to get medical care.
The current guidance from the Centers for Disease Control and Prevention recommends that you call a medical professional if you notice symptoms and
Live in or have traveled to an area with a known coronavirus outbreak
or
Have had close contact with someone who has traveled to an area with an outbreak
or
Have had close contact with anyone infected.
Call your doctor or health professional before you go. That will help him or her prepare for your visit and prevent the spread of the virus to other people in the office. Be sure to wear a mask when you go to the doctors office and when youre around other people. If you cannot find a mask, you can create a makeshift one from a scarf or T-shirt.
The C.D.C. also suggests that you avoid public transportation, ride-sharing services and taxis, and that you separate yourself from other people and animals in your home as soon as possible. That means not letting anyone enter your room and, ideally, not sharing bathrooms. Others should stay more than three feet away from you and avoid any surface you might have coughed on or touched, including doorknobs, plates, cups and towels. Disinfect the environment as much as possible.
Many state health departments have set up hotlines for people who want more information, but long wait times have been reported. Eventually, specific coronavirus testing centers may be set up.
Follow the same steps listed above if you think your children, or anyone else in your household, may be infected. Both the coronavirus and influenza are most dangerous to people who are over 65 or have chronic illnesses or a weak immune system. Children infected with the new coronavirus tend to have mild or no symptoms, and it is unclear how easily they transmit the disease to teenagers or adults.
The coronavirus seems to be more deadly than seasonal flu and quite contagious. Early estimates of the coronavirus death rate from Wuhan, China, the epicenter of the outbreak, have been around 2 percent, while the seasonal flu, on average, kills about 0.1 percent of people who become infected. But children appear to be more affected by the flu.
By contrast, the 1918 flu had an unusually high fatality rate, greater than 2 percent. Because it was so contagious, that flu killed tens of millions of people.
The new coronavirus seems to spread very easily, especially in confined spaces like homes, hospitals, churches and cruise ships. It appears to spread through droplets in the air and on surfaces from a cough or sneeze.
Whether a surface looks dirty or clean is irrelevant. If an infected person coughs and a droplet lands on a surface, a person who then touches that surface could pick it up.
A study of other coronaviruses found that they remained on metal, glass and plastic for two hours to nine days. But there is good news: The virus is relatively easy to destroy using any simple disinfectant or bleach.
Droplets can sit on the surfaces of latex gloves. Some experts suggest wearing cloth or leather gloves that absorb droplets and are bulky enough to discourage you from touching your face.
That is still unknown. This is a new virus, and everyone is believed to be susceptible.
Flu transmission decreases in hot weather every year, and the SARS coronavirus emerged in winter and was eliminated by the following June. But SARS was beaten by aggressive containment measures, not by the weather. The four mild coronaviruses that cause common colds still circulate in warm weather and cause summer colds.
In the 1918 and 2009 flu pandemics, there was a second wave in the fall.
There is no approved antiviral drug for the coronavirus, though several are being tested. For now, doctors can recommend only the usual remedies for any viral illness: rest, medicine to reduce pain and fever, and fluids to avoid dehydration.
Coronavirus patients with pneumonia may also need oxygen, and a ventilator if breathing trouble worsens. Some patients who appear to be doing well have a crash in the second week of their illness.
An experimental vaccine for the coronavirus may be ready for testing in humans within a few months. But even if it is approved, it will take much longer, at least a year, before it is available for widespread use. In the meantime, experts are urging people and their children to get a flu shot.
This virus can be deadly. Theres a reason government officials and medical experts across the world are issuing strong warnings.
About 80 percent of victims will recover without any need for hospitalization. Still, the cases categorized as mild by the Chinese C.D.C. included those with mild pneumonia, meaning there is fluid in the lungs but not seriously enough to require supplemental oxygen or intensive care. The other categories are severe, which means oxygen or ventilation is required, and critical, which means lung or organ failure.
It is important to keep these distinctions in mind, both to avoid unnecessary panic and to get a clear picture of the likelihood of transmission.
Many people are now panicking, and some actually are exaggerating the risks, said Dr. Jin Dong-Yan, a virology expert at the University of Hong Kong.
Unlike other, more mild coronaviruses, this one causes many deaths.
It is unclear how many completely symptom-free cases there are, because some people test positive a day or two before developing symptoms. The World Health Organization believes that only about 1 percent of cases never develop a fever or any other symptoms.
An office worker is screened with an infrared thermometer as he enters a building in New Delhi, India. Prashanth Vishwanathan/Bloomberg via Getty Images hide caption
An office worker is screened with an infrared thermometer as he enters a building in New Delhi, India.
Mild.
Moderate.
Serious.
Severe or extreme.
These are some of the adjectives being used to describe the symptoms displayed by patients with COVID-19. Vice President Pence used them in his remarks to the nation this week:
"Some some large percentage have mild flu symptoms; some have serious flu symptoms."
At this stage of the COVID-19 pandemic, there is not a standard definition of what symptoms are associated with these designations.
It can take years for such guidelines to be issued for a newly identified disease, according to Dr. Sandro Galea, an epidemiologist and dean of the Boston University School of Public Health.
Nonetheless, there are some preliminary definitions that can be helpful in understanding the range of symptoms.
Mild
In 80% of known cases, COVID-19 causes mild to moderate illness, according to a report of a joint World Health Organization-China mission of 25 infectious disease experts held in China late last month.
At a press conference on March 9, Maria Van Kerkhove, technical lead of the WHO Health Emergencies Program, had this to say about the symptoms for a so-called "mild" case: "This mild infection starts normally with a fever, although it may take a couple of days to get a fever. You will have some respiratory symptoms; you have some aches and pains. You'll have a dry cough. This is what the majority of individuals will have."
It is "nothing that will make you feel like you need to run to a hospital," says Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security.
A mild case of COVID-19 in and of itself is not dangerous. But in some cases more commonly in older people and in people with underlying health issues a mild case can progress to a moderate case that could require some supportive care such as fluids for dehydration, typically in an emergency room or urgent care center, especially if hospitals are overwhelmed by the most acute cases.
Moderate
Symptoms of being moderately ill with COVID-19 include coughing, fever above 100.4, chills and a feeling that you don't want to or can't get out of bed, says Adalja.
Some patients also experience shortness of breath, although that can occur in various ways. "Shortness of breath is a wide spectrum and whether we consider treatment will be based on how short of breath they are, their age and other health conditions," says Galea.
"Is it shortness of breath after climbing a flight of stairs or when there's no activity for example, when you're just sitting in a chair?" says Dr. Theresa Madaline, hospital epidemiologist at the Montefiore Health System in New York City.
In either case, there's cause for concern with a confirmed or suspected COVID-19 case. "Shortness of breath [with this virus] is a symptom to always check with a health care provider. Period," says Dr. Kenneth E. Lyn-Kew, a pulmonologist in the Section of Critical Care Medicine and Department of Medicine at National Jewish Health in Denver.
That's because shortness of breath can be caused by low oxygen levels in the blood. Blood carries oxygen to organs and tissues, and low levels can lead to organ shutdown or even death.
For patients with moderate symptoms, hospitalization is unlikely unless they are having difficulty drawing a breath or are dehydrated. Signs of dehydration can include increased thirst, dry mouth, decreased urine output, yellow urine, dry skin, a headache and dizziness.
But there's another possible development within the "mild to moderate" classification. "Some of those individuals will go on to develop a mild form of pneumonia," Van Kerkhove says. While pneumonia can often resolve on its own, especially in younger people, in older people and in those with underlying health conditions, pneumonia can be life-threatening or require hospitalization, especially if their immune system is weak.
In these instances, without supplemental oxygen or, if needed, a respirator to aid breathing, a patient's organs can shut down and the patient can die, says Galea. People with pneumonia can also get secondary bacterial infections, which can be life-threatening and require treatment with intravenous antibiotics.
A case that is "mild to moderate" will last about two weeks from the first signs of symptoms to recovery, WHO says.
Serious, severe, extreme
According to the report of the WHO-China joint mission, in about 1 in 5 patients, the infection gets worse. About 14% of cases can develop into severe disease, where patients may need supplemental oxygen. And 6% of cases become critical and may experience septic shock a significant drop in blood pressure that can lead to stroke, heart or respiratory failure, failure of other organs or death.
Theresa Madaline says that in some patients, symptoms can progress to severe in a few hours or over several days.
A different problem can occur if disease progresses. The virus can enter lung cells and start replicating, killing the cells. The immune system may take action to fight the virus, creating inflammation, destroying lung tissue and sometimes resulting in a more severe form of pneumonia.
This [immune system] response can impair your ability to get oxygen into your blood. Without enough oxygen, inflammation can become more severe and result in organ failure.
What to tell your doctor about symptoms
"Keep in mind that mild, moderate and severe are the inelegant terms we have right now," says Dr. Shira Doron, hospital epidemiologist at Tufts Medical Center in Boston. "Use symptoms rather than adjectives when you speak to a health care provider" and then they can determine whether you need to consider treatment.
The US Health and Human Services Department was the victim of a cyberattack yesterday, the agency confirmed to Recode.
Bloomberg, which was first to report the attack on Monday morning, initially described it as a hack, but updates to its story removed the word hack, instead referring to it as multiple incidents of a cyber intrusion. A subsequent ABC News story said it was actually a distributed denial of service (DDoS) attack, which is a type of cyberattack but not a full breach. A DDoS attack is more consistent with Bloombergs description, which said the agencys servers were overwhelmed with millions of hits designed to slow or shut them down. Both reports said the attack was not successful and that no data was accessed.
Caitlin B. Oakley, a spokesperson for the HHS, told Recode that there was a significant increase in activity on HHS cyber infrastructure but that it remained fully operational.
Early on while preparing and responding to Covid-19, HHS put extra protections in place, Oakley said. HHS has an IT infrastructure with risk-based security controls continuously monitored in order to detect and address cybersecurity threats and vulnerabilities.
Meanwhile, the National Security Council confirmed to Bloomberg that there was an incident but downplayed its impact, adding that HHS and federal networks are functioning normally at this time.
We are aware of a cyber incident related to the Health and Human Services computer networks, and the federal government is investigating this incident thoroughly, John Ullyot, NSC spokesperson, said in a statement to Bloomberg. HHS and federal government cybersecurity professionals are continuously monitoring and taking appropriate actions to secure our federal networks.
In a Monday morning tweet, Washington Post reporter Ellen Nakashima said that a Department of Homeland Security source told her the attack has been overblown and that the site never crashed or seemingly was in any danger of doing so.
Details of the cyberattack at HHS emerged at the same time as a flurry of reports about a foreign disinformation campaign designed to spread fear during the coronavirus pandemic. Three anonymous federal officials told the Associated Press that such an effort was underway, though they did not specify which foreign entity was leading the effort. Bloomberg also reported that a recent tweet referencing a misinformation campaign from the National Security Council was related to the attack:
But its not entirely clear how the two incidents are related. The NSC tweet appears to be a reference to a viral text message that says President Trump is on the verge of declaring a nationwide mandatory quarantine a rumor that the White House has denied. It also seems as though such an action by the president would not be constitutional, since theres little evidence that a DDoS attack would result in the spread of misinformation.
An attack on the HHS during the coronavirus pandemic is probably not a coincidence, and now is obviously one of the worst possible times for an elevated level of uncertainty and fear. According to Bloomberg, officials dont yet know who is responsible but are assuming its a hostile foreign actor.
So far, its hard to know how seriously to consider the threat of further cyberattacks. DDoS attacks are common as cyberattacks go, because they are relatively easy. Where DDoS attacks that flood a server with messages can be performed with a single computer, a more powerful DDoS requires a network of computers or botnets. Over the course of the past decade, these types of attacks have become increasingly popular as tools of political protest or weapons of disruption. As long as the attacker has enough bots in their arsenal, they can temporarily devastate their victim websites, which may be forced offline for hours or even days an outcome that would have been particularly harmful in this case but, fortunately, appears to have been avoided.
While it doesnt look as though the HHS attack did more than spread fear, cybersecurity researchers have warned of several coronavirus-related phishing campaigns and malware posing as official emails or websites from health organizations. Those threats, along with the possibility of a foreign disinformation campaign, serve as additional evidence that were only just beginning to comprehend the scope of the coronavirus pandemic and its consequences.
]]> Janssen works on Covid-19 vaccine and treatments. Credit: Janssen Cilag.
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Johnson & Johnson (J&J) subsidiary Janssen Pharmaceutical has partnered with the Beth Israel Deaconess Medical Center (BIDMC) to advance Covid-19 vaccine development.
The partners started preclinical testing of different vaccine prospects. The aim is to select a vaccine candidate for clinical trials by the end of this month.
Janssen expects to launch a Phase I clinical trial by the end of the year. The company is also working to upscale production and manufacturing capacities to meet public vaccination needs globally.
J&J chief scientific officer Paul Stoffels said: It is critical to work with the best scientific minds as we look to rapidly identify and develop solutions to the Covid-19 outbreak. We are grateful for talented and experienced collaboration partners like Dan Barouch and his team at BIDMC.
By mobilising our collective resources, we believe we can leverage the top science and cutting-edge capabilities to respond to this pandemic.
For the Covid-19 vaccine project, Janssen is leveraging its AdVac and PER.C6 technologies that enable rapidly upscale production.
The company is using its vaccine technology also utilised to create its investigational Ebola, Zika, RSV and HIV vaccines.
BIDMC Center for Virology and Vaccine Research director Dan Barouch said: We are currently evaluating a series of potential vaccine candidates for Covid-19.
This collaboration with Janssen is aimed at the development of a Covid-19 vaccine that would allow for rapid development, large-scale manufacturing, and global delivery.
In February, Janssen collaborated with the US Department of Health & Human Services (HHS) to develop an investigational vaccine candidate against coronavirus.
Later, the alliance was expanded to discover effective Covid-19 therapies.
Nothing can stop a global outbreak in its tracks better than a vaccine. Unfortunately, creating a vaccine capable of preventing the coronavirus that causes COVID-19 will probably take at least a year to 18 months, health officials say.
That is the time frame, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told the House Oversight and Reform Committee this week. Anyone who says they can do it faster will be cutting corners that would be detrimental.
While there are about 10 vaccine candidates in the works and at least one of them could begin clinical trials in April it would still take about three more months to conduct the first stage of human testing and another eight months or so to complete the next stage of the trial process, he added.
New vaccines require copious research and time-consuming testing that can cost hundreds of millions of dollars. Theres no guarantee of success, but even if everything goes well, the final product might not hit the market until after an outbreak has subsided.
Heres a look at how vaccines are made and why the process takes so long.
Your body has a multi-pronged defense system for recognizing and combating dangerous invaders: your white blood cells. There are several types, each with a different purpose:
Macrophages engulf and then eat pathogens or cells that are dead or damaged. They leave behind identifying fragments of the invading microbes. These fragments are called antigens.
B-lymphocytes produce antibodies that recognize and bind to those antigens. If a pathogen with those antigens shows up in the blood stream again, those antibodies can mount an attack.
If those pathogens are already hiding out inside your cells beyond the antibodies reach, T-lymphocytes can attack those infected cells.
Your immune system has to go through this process each time it encounters a threat from a new virus or bacterium.
A vaccine provides a shortcut. Essentially, it helps your immune system learn to recognize a specific threat by tricking it into thinking its under attack. Then it can produce the antibodies it needs without having to face a real infection.
Nope. The Centers for Disease Control and Prevention describes several types of vaccines:
Attenuated vaccines, like those for chickenpox and measles, use a live virus or bacteria that has been intentionally weakened so that it cant cause serious disease in a healthy immune system.
Inactivated vaccines, such as the one for polio, use germs that have been killed. They typically dont provide as much immunity as attenuated vaccines, so they may require boosters over time.
Toxoid vaccines, including the DTaP vaccine for diphtheria and tetanus, use weakened versions of the toxins created by invading bacteria to teach the body how to fight the pathogens.
Subunit vaccines, such as DTaPs whooping cough component, only use fragments of the virus or bacterium they protect against.
Conjugate vaccines teach the immune system to fight bacteria that try to disguise their antigens in the long chains of sugar molecules that form the walls of bacterial cells.
The immune system learns how to fight a virus by studying its face the outside of the particle, including those telltale antigens. So a vaccine needs to give your body a snapshot of that face.
One classic technique involves injecting a person with a killed virus. Another uses live viruses that have been grown and deliberately weakened, typically by removing specific genes in their RNA or DNA.
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Both of these strategies take some time, and scientists worry that if they use them on novel viruses, they may not behave the way researchers predict, said Dr. Kathryn Stephenson, who runs the clinical trial unit at Beth Israel Deaconess Medical Centers Center for Virology and Vaccine Research.
Another option for scientists is to reconstruct that snapshot using information from a virus genetic code, which may be made of either RNA or DNA.
Nowadays, researchers can get started fast. Scientists in China made the coronavirus RNA sequences available on Jan. 10, and many labs began working toward a vaccine the next day, Stephenson said.
Hardly. Designing the vaccine is just the first step. Then it has to be produced.
There are many different vaccine-making platforms, each with its own set of advantages and disadvantages.
What would make a great vaccine for coronavirus is one that you can make quickly and one that would provide long-lasting and effective immunity, Stephenson said. Those are not always the same thing.
For example, a vaccine based on the virus genome can be made quickly, in perhaps a month or two, but it may be harder to manufacture in giant quantities.
Another option is to take the virus genetic snapshot and put it into a different virus for transport. When introduced into the body, the so-called viral vector vaccine enters cells, prompting them to produce huge numbers of this snapshot for the immune system to see. These vaccines take longer to make say, six to eight months but they can be scaled up more readily.
A lot of us are working on both of those, Stephenson said.
Before a vaccine candidate is approved for use, it must be proven safe and effective in a series of trials that are monitored by the Food and Drug Administration.
The first step is to show that its safe in preclinical studies. These can be conducted in vitro (using cells in a laboratory dish) or in vivo (using an animal as a stand-in for humans). Finding the right animal for testing can be a challenge, said Robert Grenfell, director of health and biosecurity at CSIRO, Australias national science agency, but scientists working on a vaccine for the new coronavirus wont have to start from scratch. The new virus shares much of its genome with the coronavirus that caused the 2003 outbreak of severe acute respiratory syndrome, and some Australian researchers already have been studying the SARS virus in ferrets.
Then clinical trials in humans can begin. Phase 1 trials are small, usually with a few dozen closely monitored participants. The main goal here is to make sure the vaccine is safe. Phase 2 trials typically enroll hundreds of patients to expand the safety assessment and allow scientists to dig into the bodys immune response. Phase 3 trials can enroll thousands of people, typically with some of them randomly assigned to get the vaccine and some getting a placebo.
This process can take years under normal circumstances. In an emergency, it could be sped up dramatically.
The big sticking point is often the Phase 3 trial. In an epidemic, many study volunteers may not want to risk getting a placebo instead of the vaccine, Stephenson said.
Researchers faced this dilemma during the Western African Ebola outbreak that took off in 2014. The virus had a mortality rate of about 40%, making people desperate for the still-unproven vaccine. So researchers employed a novel experimental design that involved vaccinating people with varying degrees of separation from an Ebola patient and using computer models to help determine if the vaccine had had an effect.
I think people learned from that that there are ways to be creative, Stephenson said. A creative solution may be needed when a coronavirus vaccine is ready for Phase 3 testing, she added.
The FDA wants it to be both safe and effective in other words, it has to protect enough people with as few unwanted side effects as possible. But exactly what qualifies as safe and effective may depend on the disease in question.
For some perspective: Stephenson, who also studies HIV, said that researchers would be very happy if they could come up with an HIV vaccine that protected 50% or so of those who got it. On the other hand, for a highly contagious virus like measles, a vaccine would need to work in almost everyone to establish herd immunity, she said.
David Weiner, a molecular immunologist who directs the Wistar Institutes Vaccine and Immunotherapy Center, said a successful coronavirus vaccine wouldnt have to be 100% effective.
I would like us to see it work in the majority of people, he said, but if it worked in 50%, 50% is a big improvement over 0%.
Definitely not. The labs that create a successful vaccine probably wont be the ones that are able to scale up theyll need a dedicated manufacturer for that part. And many companies may be wary of investing the resources it takes to manufacture a new vaccine when the epidemic could end before theres a chance to bring it to market, Weiner said.
Big Pharma is afraid to go in because the outbreaks end and they lose all the money they put in, he said. Thats why the Oslo-based Coalition for Epidemic Preparedness Innovations, or CEPI, has stepped in with funding to help shepherd some of those efforts, he added.
One of the big technical challenges in large-scale manufacturing is quality control, Stephenson said.
Every vaccine has its own particular issue, she said, but the manufacturing challenges mainly have the most to do with safety precautions and making sure that when youre done, the vial of vaccine has in it what you say it has.
This can be a difficult question when theres a limited amount of vaccine and a whole lot of demand.
Since older adults appear to be most at risk from COVID-19, its likely that health officials would focus on them first, Stephenson said.
Medical professionals who are both at high risk of exposure and are needed to care for those who are sick would likely be a priority as well.
Front-line healthcare workers are usually one of the first groups you vaccinate because you need your workforce in place, she said.
Vaccines are often less effective in older people than they are in younger ones, and this could affect the way that a vaccine is administered. A vaccine might be given in multiple doses, or an adjuvant might be added to it to boost the immune systems reaction to it.
The CDC suggests some common-sense ways for people to protect themselves:
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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 in April.
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, and is collaborating with Cepi over a Covid-19 vaccine.
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.
