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FDA Actions

FDA-ARGO SARS-CoV-2 Reference Grade Sequencing Data: The FDA has partnered with Centers for Disease Control and Prevention (CDC), the Biodefense and Emerging Infections Research Resources Repository (BEI Resources) and the Institute for Genome Sciences at the University of Maryland and the National Center for Biotechnology Information (NCBI). Together they have developed reference sequence data for the SARS-CoV-2 reference strain for the U.S.

Warning Letter: The FDA and FTC issued a warning letter to Neuro XPF with providing misleading claims that its products can prevent, treat, diagnose or cure COVID-19.

Diagnostics Update: The FDA has worked with more than 220 test developers who plan to submit EUA requests to detect COVID-19. Also, 23 EUAs have been issued. The FDA has been notified that more than 110 laboratories have begun testing under the policies set forth in its COVID-19 Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency Guidance.

Diagnostics

MicroGenDX Laboratories’ rRT-PCR assay for SARS-COV-2 received EUA from the FDA. It is the first test validated using saliva and sputum samples.

Regeneron is making $1 million worth of a liquid that preserves swab samples taken during COVID-19 testing. Workers in Regeneron’s East Greenbush manufacturing facility have been volunteering hours to help make this key component for COVID-19 test kits.

LifeSignals Group Inc. announced that a single-use, wireless biosensor patch for the early detection and monitoring of coronavirus symptoms is being fast-tracked for introduction within weeks. The patch, which is affixed to the the chest, will record temperature, respiration rate, ECG trace, heart rate and movement in real-time.

Testing Therapies, Antivirals and Vaccines

Pinpoint Therapeutics: Pinpoint Therapeutics believes that its approach to treat therapy-resistant cancers also may be effective against COVID-19. The molecule Pinpoint is developing, dimeric chloroquine, targets PPT1, an enzyme in the autophagy pathway that tumors use to block therapeutics. CEO Christian Peters, M.D., Ph.D., believes targeting this pathway and, specifically, the PPT1 enzyme, could prevent the COVID-19 virus from entering cells to cause infections.

Noxopharm: Australian-based Noxopharm, announced it has identified a clinical trial opportunity to help reduce the mortality rate of COVID-19. In preclinical research, idronoxil inhibits a range of inflammatory mediators known as cytokines, including interleukin-6 (IL-6) that are involved in a process known as a cytokine storm.

APEIRON Biologics AG: APEIRON announced it has received regulatory approvals to initiate a Phase II clinical trial of APN01 to treat COVID-19. Approvals were in Austria, Germany and Denmark. APN01 has the potential to block infection of cells by COVID-19 and reduce lung injury.

BioAegis Therapeutics Inc. believes its lead product, recombinant human plasma gelsolin therapy (rhu-pGSN), should be considered as a viable therapeutic option for patients suffering from severe lung injury due to COVID-19. The company is submitting requests to the FDA and other international regulatory authorities to accelerate their clinical trial. The company’s asset, rhu-pGSN, disrupts the course of inflammatory and infectious diseases which very often can lead to long term morbidity or death. 

Altimmune, Inc. and the University of Alabama at Birmingham will collaborate on the development of a single-dose, intranasal COVID-19 vaccine, called AdCOVID. It is expected that AdCOVID has the potential to activate multiple arms of the immune system as shown in a recent Phase II clinical study with NasoVAX, an influenza vaccine candidate based on the same platform technology, the company said.

Swiss pharma company Neurimmune and Germany’s Ethris GmbH forged a partnership to develop mRNA-encoded, neutralizing anti-SARS-CoV-2 antibodies administered by inhalation for the treatment of COVID-19. The collaboration brings together Neurimmune’s expertise in developing human antibodies based on high-throughput immunoglobulin sequence analyses from COVID-19 patients who have recovered from the disease with Ethris’ proprietary and unique pulmonary SNIM RNA therapeutics platform.

CytoDyn’s leronlimab continues to show positive response in COVID-19 patients, with a “significant trend toward immunological restoration.”

CAS, a division of the American Chemical Society specializing in scientific information solutions, released an open-access dataset of chemical compounds with known or potential antiviral activity to support research, data mining and analytics applications. The new CAS COVID-19 Antiviral Candidate Compounds Dataset contains nearly 50,000 chemical substances extracted from the CAS REGISTRY that have antiviral activity reported in published literature or are structurally similar to known antivirals.

Ennaid Therapeutics: Ennaid announced that it is advancing the development of ENU200, as a therapeutic to treat the up to 80% of asymptomatic, mild to moderate cases of COVID-19 infections.

Celularity: Celularity announced the FDA has cleared the company’s Investigational New Drug (IND) application for use of its CYNK-001 product in adults with COVID-19. The company will commence a Phase I/II clinical trial including up to 86 patients with COVID-19.

Company Actions

OSE Immunotherapeutics: A late-stage lung cancer drug under development by OSE Immunotherapeutics met its 12-month primary endpoint for survival rates following a Step-1 analysis. But, the ongoing COVID-19 pandemic is causing the company to rethink its ongoing clinical plans for the drug.

Vir Biotechnology and Alnylam Pharmaceuticals expanded their multi-target existing collaboration for RNAi therapies for infectious diseases to include COVID-19. It will include up to three additional targets for host factors for SARS-CoV-2, including ACE2 and TMPRSS2.

Momenta Pharmaceuticals’ trial updates: Phase II VIVACITY-MG study of nipocalimab in generalized myasthenia gravis is fully enrolled and continuing; its Phase II UNITY trial of nipocalimab in hemolytic disease of the fetus and newborn (HDFN) continues to enroll patients at sites where it can be done and doesn’t intend to pause enrollment because of the life-threatening nature of HDFN, but does expect a slower pace of enrollment; its Phase II/III Energy Study of nipocalimab in warm autoimmune hemolytic anemia (wAIHA) is activating sites, but has temporarily suspended patient enrollment; and its M254 for intravenous immunoglobulin Phase I/II study in idiopathic thrombocytopenic purpura continues to enroll lower dose cohorts, but most of the sites have suspended enrollment.

Fulcrum Therapeutics noted its ReDUX4 trial for Facioscapulohumeral Muscular Dystrophy is fully enrolled, but because some of the clinical sites are closed, the company is assessing its timeline for topline data.

Applied Therapeutics announced its COVID-19 IND has been opened with the FDA for AT-001, a novel potent Aldose Reductase inhibitor in Phase III development for diabetic cardiomyopathy. It is being evaluated for acute lung inflammation and cardiomyopathy in critical COVID-19 patients.

Amgen and Adaptive Biotechnologies team to develop an antibody therapy against COVID-19.

Fluidigm Corporation’s Fluidigm CyTOF technology was used in a clinical trialthat provided preliminary data that mesenchymal stem cell (MSCL) therapy improved outcomes in COVID-19 pneumonia. Data was published by Chinese researchers in Aging and Disease.

Geron Corporation indicates that its IMerge Phase III trial is ongoing, but there have been delays because of the pandemic. On a positive note, because of the slower completion and enrollment, it expects its 2020 operating expense burn to be lower than previously indicated.

Spring Bank Pharmaceuticals reports that its Phase Ia/Ib trial of SB 11285 in solid tumors is continuing, although some institutions involved have suspended patient enrollment. The company indicates sit is reviewing its portfolio of RIG-I agonists from its STING platform for COVID-19. These compounds have shown activity against viral respiratory diseases such as RSV, influenza and parainfluenza.

Pfizer, Merck & Company and Eli Lilly and Company will allow employees who are licensed medical professionals to aid in the fight against COVID-19 while maintaining their base pay from the companies. The three companies employ thousands of doctors, nurses, pharmacists, medical laboratory technicians and other medical professionals whose services are in high demand during the COVID-19 pandemic.

Other Industry News

Elizabeth Holmes’ legal team is seeking special exemptions from the court for COVID-19-related stay-at-home orders in California in order to meet a July trial deadline. But, the judge denied that request due to safety concerns and, for now, refused to delay the start of the trial for wire fraud.  

Compare: 1918 Spanish Influenza Pandemic Versus COVID-19. With all the similarities, it should be emphasized that there are several significant differences between the two pandemics.

Medical school didn’t teach me how to decide which of my patients should live and which should die if it becomes rationing of medical equipment or treatment becomes necessary. But I’ve spent most of my time recently planning for the possibility that my colleagues and I may need to make precisely that decision.

Reports have emerged from Italy about doctors choosing who would receive lifesaving medical care and who would not. New York’s governor, Andrew Cuomo, pleaded this week for 30,000 ventilators, three times the 10,000 ventilators currently available. As I write this, there are more than 80,000 confirmed cases of Covid-19 in the United States. If the number of people with severe cases outstrips the number of ventilators, will doctors decide who gets one?

Even though the U.S. is one of the richest countries in the world, rationing health care is not new here.

In the 1960s, people living with kidney failure fought for a limited number of dialysis machines. At first, panels considered “social worth” when deciding who got dialysis. This injustice led to federal funding for dialysis for all Americans with kidney failure. But money doesn’t solve all problems. As a doctor who cares for critically ill patients, I have seen countless children die waiting for a liver or heart transplant. Every day 20 Americans die while waiting for an organ transplant, a kind of decision-less rationing. When resources are scarce, hard decisions must be made.

The Covid-19 pandemic is already forcing hard decisions. Doctors in New York City are delaying surgeries for patients, some of whom may die waiting. Some hospitals have changed infection-control policies to reserve personal protective equipment, risking the transmission of other difficult-to-control infections. While many systems have transitioned to telehealth, canceling clinics to promote social distancing means that some will go without needed medical care.

On March 25, the federal government agreed to provide $2 trillion in financial reliefbecause of Covid-19 but, again, money may not solve the problem.

As the director of the Center for Bioethics and Medical Humanities at Northwestern University, I am one of many people planning for who gets the next available ventilator if supplies are limited and rationing becomes necessary. Here is what you should know about those plans and how they are being made:

First, past health care crises like the Ebola outbreaks, severe acute respiratory syndrome (SARS), and the H1N1 influenza pandemic prompted much advance planning. In 2012, the Institute of Medicine published guidance for what to do in a crisis like Covid-19. Many states used this report to create their own plans, including Illinois, where I practice. Importantly, input from the public is also available.

Second, bioethicists, clinicians, and health care leaders across the country are sharing information to help provide consistency from one hospital to another. Douglas B. White, who directs the Program on Ethics and Decision Making in Critical Illness at the University of Pittsburgh School of Medicine, and Scott Halpern, professor of medicine at the University of Pennsylvania, have circulated a plan based on a process published in a top medical journal that hundreds of hospitals across the country are using as a guide. In some areas, statewide plans are being implemented. To be sure, sharing doesn’t ensure consistency. But it will certainly help.

Third, every plan should support shared ethical values. This means starting with the idea that every life is worth saving and that the goal is to help the most people possible. To accomplish this, many plans use a scoring system based on objective information about each patient’s medical condition. Using a scoring system to help predict who will survive helps avoid biased decision-making.

Of course, no scoring system is 100% accurate. And many people worry that certain groups with underlying health problems, including those who are disabled, homeless, incarcerated, or poor, are disadvantaged by such scoring systems. And even with a scoring system, there needs to be a plan for breaking ties.

Fourth, a physician’s ethical duty is to care for his or her patients. If I am taking care of two patients in the intensive care unit who both need a ventilator, I should not be the one to decide who gets the machine. That decision should be made by others, preferably a group of medical experts who don’t know anything about the patients involved except the facts they are given.

Fifth, not using lifesaving treatments does not mean we stop caring. For those who may not survive, palliative care is essential to help relieve pain, difficulty breathing, and other symptoms, and support psychological and spiritual distress.

Finally, resources are available for how these decisions might be made. The New England Journal of Medicine recently published articles about allocating ventilatorsand rationing scarce resources. The Hastings Center, a nonpartisan, nonprofit organization, has an entire website on the ethics of resources during Covid-19.

I have had to learn many lessons about being a doctor since finishing medical school. I wish this wasn’t one of them.

Kelly Michelson, M.D., is director of the Center for Bioethics and Medical Humanities at Northwestern Feinberg School of Medicine and a physician in the pediatric intensive care unit at Ann & Robert H. Lurie Children’s Hospital of Chicago.

Every strategy for releasing Covid-19’s vise-grip on daily life starts with identifying cases and tracing their contacts — the laborious task of public health workers tracking down people who have crossed paths with a newly diagnosed patient, so they can be quarantined well before they show symptoms.

That typically takes three days per new case, an insurmountable hurdle in the U.S., with its low numbers of public health workers and tens of thousands of new cases every day. Existing digital tools, however, using cellphone location data and an app for self-reporting positive test results, could make the impossible possible, the authors of a new analysis argue.

“Traditional manual contact tracing procedures are not fast enough for [the new coronavirus],” researchers at the University of Oxford write in a paper in the journal Science this week. But digital technology“can make contact tracing and notification instantaneous.”

The “technology to the rescue” idea has been gaining steam as the coronavirus pandemic has outpaced everything Europe and the U.S. have thrown at it, and not because of a deluded belief that digital tech can solve all the world’s woes. Instead, this fix is aimed at a very specific problem: identifying cases of Covid-19 and quickly tracing everyone who came into contact with them before they infect others. That has helped countries such as South Korea, Taiwan, and Singapore beat back the epidemic, though sometimes through measures that trample privacy.

“We have evidence that this works,” said computational epidemiologist Maia Majumder of Boston Children’s Hospital, referring to contact tracing and case isolation. “The public health consensus is clear that this is what we need to do.”

The U.S. and Europe have hardly attempted contact tracing, however. It requires an army of public health workers or intrusive policies that many of their citizens oppose. But this week brought efforts to circumvent both obstacles.

One high-profile effort is led by Trevor Bedford, an infectious disease modeler and genomics expert at the Fred Hutchinson Cancer Research Center in Seattle. This week, he and his colleagues launched “NextTrace,” a project based on the fact that traditional contact tracing doesn’t scale: With more than 200,000 cases in the U.S., and each case requiring hours of detailed follow-up, doing this by analog methods won’t work.

“So much of this virus’s transmission, maybe 15% of total cases, is from people who don’t feel sick,” said mathematical biologist Lauren Ancel Meyers of the University of Texas at Austin, who is advising NextTrace. “And it’s spreading so quickly, with as few as four days from when one person shows symptoms to when people he infects does. It would therefore take a heroic effort and very fast quarantine and isolation to identify, by traditional methods, every person who’s infected, and every person they contact, and everyone they contact.”

NextTrace therefore plans to build a decentralized reporting system in which anyone with confirmed Covid-19 can choose to register, anonymously, on an online platform. The platform will use cell phone location and proximity data from cellphones, for people who have opted in, to find individuals who might have been exposed to this case and advise them to be tested. The system would build a contact history for each case.

Exposed individuals can be tested and, if infected, isolated. The earlier that happens the more transmission drops: People shed the highest level of virus soon after symptoms appear, scientists in Germany reported on Wednesday in the journal Nature.

Johnson & Johnson has announced plans to team up with the US government to invest more than  $1 billion in a new vaccine against COVID-19, aiming to begin clinical trials by September.

Medical devices giant Abbott has also helped the effort against the coronaviruspandemic with a fast test kit, which could be an important development in the US where there is a national shortage of tests.

In January, J&J was one of the first companies to announce it had started work on a vaccine after Chinese scientists published the genetic code of the SARS-CoV-2 virus that causes the disease.

Now the company’s Janssen unit said it has identified a suitable vaccine candidate and has expanded an existing partnership with the US government agency the Biomedical Advanced Research and Development Authority (BARDA).

The goal is to provide a global supply of more than a billion doses of a vaccine, with trials starting in September at the latest, and the first batches potentially available for emergency use in early 2021.

Although J&J said this was a “substantially accelerated timeframe”, Moderna was the first US firm to announce it had begun vaccine trials earlier this month.

China’s CanSino Biologics, working with the Beijing Institute of Biotechnoloy, has also begun a clinical trial of a vaccine.

J&J and BARDA have committed more than $1 billion of investment to co-fund development, with the big pharma using its validated vaccine technology and allocating resources, personnel, and infrastructure accordingly.

BARDA and J&J have provided additional funding to expand their ongoing work to identify potential antiviral treatments against the novel coronavirus.

J&J will also expand its manufacturing operations in the US and in other countries so that the company is able to keep pace with demand.

Including preclinical efforts a COVID-19 therapy tracker from the Milken Institute lists more than 30 vaccines against COVID-19 under development.

Five minute test

In a separate development medical devices firm Abbott said the FDA had backed its five-minute COVID-19 test, which uses its ID NOW platform to provide fast results in hospitals, doctors’ offices, urgent care clinics and emergency departments.

The FDA has granted an Emergency Use Authorization (EUA) to allow the tests to be used on ID NOW, which is the size of a small toaster and is already the most widely available point-of-care testing platform in the US.

Tests will be available next week, as the US healthcare system struggles with a shortage of tests for the coronavirus.

The shortage of tests in the US stems from a decision by US authorities to run with a test developed by the Centers for Disease Control instead of using a protocol developed by the World Health Organization when the epidemic began to take off in January.

Unfortunately the CDC test was found to be inconclusive shortly after it reached labs, and the US has been playing catch-up since then, CNN reported.

Consumers in the UK will be able to log onto either Amazon or Boots’s website to order a home test for delivery that will tell them whether they have had the coronavirus, according to a press report.

According to the report, Amazon’s tie-up with Boots is an important development in the effort against the coronavirus, as well as a landmark in the online retail giant’s move into healthcare.

The home test kit works by pricking the user’s finger for blood, which is tested for the presence of antibodies against the virus.

Results take around 15 minutes and a positive result indicates in theory whether a person has had the coronavirus and recovered, and is unlikely to develop symptoms again after becoming immune.

The UK government has also ordered 3.5 million of the tests and is assessing their accuracy before they are made publicly available.

Lucy Ingham, Technology Editor at GlobalData’s Verdict, said: “This is a key step in the UK’s fight against the coronavirus, but for Amazon, it also represents a fortuitous step towards its wider move into the healthcare space.

“Although the US tech giant has generally declined to discuss the matter, it has been widely acknowledged that Amazon is making a slow but ambitious bid to become a key player in the healthcare space, not only in the UK, but in key markets across the world.”

Amazon has not publicly commented on the story.

Mass testing is seen as the best way out of the current lockdown situation in the UK, with experts urging the government to adopt the “track and trace” approach used in South Korea to stop the virus spreading in the coming weeks.

Employees working for Amazon in the US, and its rival Instacart, have gone on strike demanding protective gear and hazard pay as they work through the pandemic.

Medbelle offers COVID-19 test

Digital hospital Medbelle is offering an in-home COVID-19 test at cost price to support the UK healthcare system, with the option for people to additionally “sponsor” tests for key workers and those in need.

The London and Berlin-based startup said its test uses a method of analysis approved and recommended by the World Health Organisation (WHO) known as RT-PCR.

Although each test costs £225, the company says this is cost price and is not looking to make a profit, aiming to ease the pressure on the health service and increase availability of testing.

The digital hospital’s test uses a method of analysis approved and recommended by the World Health Organisation (WHO) known as RT-PCR.

This involves taking a swab from inside the mouth and nose and sending it off to a lab to test for signs of the virus. This testing process is the same as the one used in the NHS, and the lab is certified by UK technical body UKAS.

The lab has already applied for specific COVID-19 certification with UKAS and Public Health England.

Tests will be posted via Royal Mail, or can be couriered in London for an additional fee

With Europe and the United States locked in deadly battle with the coronavirus that causes Covid-19, a number of countries that were hit early by the virus are doing a far better job of beating it back.

China, which is now diagnosing more cases in returning travelers than in people infected at home, reported no new domestically acquired cases on Wednesday, for the first time in more than two months. South Korea, which had an explosive outbreak that began in February, is aggressively battering down its epidemic curve. Singapore, Hong Kong, and Taiwan have together reported only about 600 cases.

Those successes have been bought by a layering of what are known as non-pharmaceutical initiatives — including social distancing and travel restrictions — aimed at severing chains of transmission to keep the virus from going into an exponential growth cycle.

None of the other countries has been as aggressive as China, which put tens of millions of people into forced quarantine for weeks. And these other locales have not all adopted an across-the-board checklist of measures. While kids in Hong Kong haven’t been in school since late January, class continues in Singapore.

Here’s a look at some of the techniques these governments employed, and how they stack up to steps being taken in the United States as well as the United Kingdom, which has come under heavy scrutiny for its approach, fairly or not.

Let’s start with Singapore.

The island city-state was one of the first places to ban incoming flights from the Chinese city of Wuhan, where the virus originated. And it placed people coming into the country from countries affected by Covid-19 into mandatory quarantine.

Singapore has seen its numbers gradually tick up. But it hasn’t had an explosion of cases, likely because it has aggressively tracked where the virus was circulating. Of the 345 cases it has recorded, 124 have recovered and 221 are considered active cases. It has not yet recorded a death.

“Singapore has done everything right,” said David Heymann, who led the World Health Organization’s response to the 2003 SARS outbreak and now teaches infectious diseases epidemiology at the London School of Hygiene and Tropical Medicine. “They’ve been openly communicating every day on what’s going on. And they’ve made it clear to the population and the population understands that they are not only to protect themselves but protect others.”

Health authorities have severed several transmission chains, tracking down people who have been in contact with a known case and ordering them into home quarantine. They are checked twice daily to see if they developed a fever.

Mass gatherings were canceled. Schools have not been closed, though students go through temperature screening to enter. So does anyone entering most buildings or restaurants.

Heymann, who was in Singapore recently to lecture at Saw Swee Hock School of Public Health, said at the start of each class, a picture would be taken of the classroom, so that if any student became ill, there would be a record of who had been in close contact with him or her. “So there’s all kinds of innovations and measures going on,” he told STAT.

Singapore also quickly developed a much-needed serology test — a blood test used to look for antibodies in blood that are a sign of previous infection. Getting a handle on how many people have been infected is critical to understanding how deadly this virus really is, experts stress. Authorities in Singapore actually used the serology testin late February to find the source of a cluster of cases in a church group.

How about Hong Kong?

Hong Kong, like Taiwan and Singapore, bears deep psychological scars from the 2003 SARS outbreak. Hong Kong had the most cases of the disease outside of mainland China and people there remember the trauma that came with it.

So do their public health leaders, who have prepared for disruptive infectious diseases outbreaks in the years since SARS and the 2009 H1N1 flu pandemic. People take respiratory health hygiene seriously, routinely wearing surgical masks in public if they are sick to prevent spread to others.

“These places were better equipped to face an outbreak of the new coronavirus than many others,” Ben Cowling, a professor of infectious diseases epidemiology, and Wey Wen Lim, a graduate student in infectious disease epidemiology at the University of Hong Kong, wrote in a recent opinion piece in the New York Times.

Hong Kong responded very quickly — within days of China’s Dec. 31 announcement that it was finding unusual cases of pneumonia. Doctors were told to report any patient who had influenza-like illness and a travel history to Wuhan. Borders crossings into China were closed — first some, then all.

Schools and universities haven’t been open since the Lunar New Year, on Jan. 23, though online learning has replaced classroom teaching in some circumstances.

Hong Kong has been testing for the virus, aggressively trying to locate cases. People have been urged to telework if possible and to practice social distancing.

Gabriel Leung, dean of medicine at the University of Hong Kong, said measures have largely worked, but the toll is high. And both he and Cowling are concerned people are starting to let down their guard.

“I think we are already beginning to see a little bit of response fatigue among the people,” Leung said, noting it has become apparent over the past couple of weeks. “You see that people are beginning to mix again, they’re beginning to come out again, because it’s been two months already. So how do you still keep alert and keep this up? There is only so much that any population would be able to tolerate.”

What of Taiwan?

Taiwan didn’t move initially to cut off air travel with Wuhan, as Singapore did. But doctors boarded incoming flights with temperature scanners looking for people who were unwell. Later it did ban most flights from China.

Mass gatherings were not banned, but were discouraged. The government controlled the distribution and pricing of medical masks, Cowling and Lim wrote. Stiff fines — up to more than $30,000 — were threatened for people who violated home quarantine orders.

“All of these places are coupling aggressive testing strategies to identify cases, with isolation, contact tracing and sometimes quarantine of at-risk people,” said Caitlin Rivers, an assistant professor of epidemiology at the Johns Hopkins Center for Health Security, speaking of Singapore, Taiwan, Hong Kong, and South Korea. “And they have also layered on community mitigation strategies, school closures … and other closures. So what I take away from that is that it’s important to layer these strategies to try to accommodate both of them.”

Rivers tried to look at whether the measures were being successful at driving down new infection rates by pulling up data on other types of communicable infections, both respiratory illnesses, diarrheal diseases, and conjunctivitis. In a short analysisshe posted on Twitter, Rivers noted that rates of these other infections declined after stringent social distancing practices were put into place.

“The things that are also spread through close contact have fallen dramatically, and so that tells me it’s individual-level social distancing behavior that is contributing to the control,” she said.

Isn’t South Korea a different case?

Indeed, the Republic of Korea has had a different trajectory than Hong Kong, Taiwan, and Singapore.

The new coronavirus took root in a large and closely knit religious sect, a development that led to an explosive outbreak, which the other three have not experienced. As of Wednesday South Korea has reported just over 8,400 cases and 91 deaths.

But whereas Western countries that have reached numbers like those see daily and every larger rises in their case counts, South Korea’s outbreak curve has been beaten back. From a one-day high of 909 new cases on Feb. 29, South Korea has seen its daily case count rise by as few as 74 cases on Monday. That swung back up, though, on Thursday to 152.

The country is testing aggressively — more than a quarter of a million people had been tested by March 15, Foreign Minister Kang Kyung-wha told the BBC recently.

“Testing is central because that leads to early detection. It minimizes further spread and it quickly treats those found with the virus,” she said, suggesting early detection and treatment may explain why South Korea’s death rate is lower than other places with large numbers of cases.

South Korea introduced drive-through testing, allowing people to be checked for disease without even leaving their vehicles. Travelers returning from abroad have to provide contact information and report their health status for 14 days after their return via a mobile app, the South Korea CDC website reports.

It has recommended Koreans refrain from international travel at this time and urged people to avoid large gatherings and church services. Companies have been encouraged to allow workers who are able to work from home.

Can these techniques be applied elsewhere? Is it too late in places like the United Kingdom and the United States?

Many epidemiologists and mathematical modelers who have been plotting the possible trajectory of this pandemic think there is no choice but to try some of the serious social distancing measures other countries have taken.

But Marc Lipsitch, an infectious diseases epidemiologist at Harvard’s T.H. Chan School of Public Health, said the possibility of containment — stopping spread — through rigorous tracing of all contacts of known cases is not realistic. That window has closed, he said.

“I think one thing to learn from those experiences is that what’s appropriate when an epidemic is small and mostly ascertained is not appropriate when an epidemic is large and mostly not ascertained,” he said.

“I would say put in place as intense as possible social distancing and get the messaging from the White House consistent with that,” Lipsitch said. “Right away, everywhere, with the short-term goal of trying to reduce the … demand on the health care system.”

Any universities still in session should send students home, especially those living in dormitories “which are one step away from cruise ships in terms of density and poor ventilation,” he said.

Lipsitch said time is limited to make a difference.

“The data that we just assembled from Wuhan about the timing and magnitude of the peak demand for critical care shows first that it can very quickly — even without that many people being infected compared to the whole population — exceed per capita bed capacity in the United States,” Lipsitch said.

He noted there was a four-week lag between the shutdown of Wuhan and the overwhelming of critical care units. “So if you wait till you see a problem, then you have another month of agony, at least.”

It appeared that was the kind of message Britain was not heeding.

There was a huge controversy late last week when it seemed like the country intended to simply allow enough people to become infected so that the population would develop “herd immunity.”

Adam Kucharski, an associate professor of infectious diseases epidemiology at the London School of Hygiene and Tropical Medicine, said it was never the government’s plan to drive toward herd immunity; rather, there was an acknowledgment that might be what happens because the virus could be so hard to control.

“It’s not been an aim to get everyone infected as soon as possible. It’s more this really tough situation we’ve got where the options we have are probably not going to be able to fully control this in the long term,” Kucharski said.

The country has now taken a swing toward the types of early and aggressive social distancing methods other countries are trying to implement. The government is urging people with even mild symptoms to self-isolate; but Kucharski worried that message was going unheard in the din about herd immunity.

The country, he said, was trying to save some of the more difficult measures — really stringent social distancing approaches that are hard to sustain over time — for closer to when they are needed.

“It makes sense to use them, given that they’re short-term measures, use them when they’ve got the most impact,” Kucharski said. “You can’t shut down your country for months.”

Rivers suggested that was a risky approach. “I think that’s a difficult thing to time. My recommendations for the U.S. context at least, is to begin social distancing measures early,” she said.

In the United States, a tepid early response — marked by a prolonged delay in ramping up testing and a White House that initially seemed intent on playing down the scale of the threat — has given way to a war footing.

This week the White House urged Americans to embrace social distancing by not taking part in gatherings of more than 10 people. In a number of communities, restaurants are closed to all but takeout or delivery service. Some states have closed schools. The country is on edge.

But with large-scale testing capacity still coming up to speed, it remains unclear how deeply the virus has embedded itself into the country, and whether the measures people and their local, state, and national governments are trying to adopt can slow the coronavirus’ progress.

It is also unclear how long communities can sustain the dramatic lifestyle changes that appear to be needed to slow the virus’s spread.

“Right now people are approaching this if they are basically sheltering in place for … a Minneapolis blizzard, lasting two or three days. And that’s the mindset that they have. Where, in fact, we need to look at this like a coronavirus winter, where we’re only in the first weeks of what could be a long season,” warned Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy.

“This could last easily many months. And we need to make our actions proportional to the risk in the community or else we run the risk of people just getting tired of them when that particular community has not seen increased transmission of the virus.”

Researchers at two prominent California universities launched ambitious new studies this week to test whether wearables can serve as a sort of early-warning system for parts of the country not yet flooded with coronavirus cases.

University of California, San Francisco, researchers are exploring whether an algorithm fed with data from Oura smart rings can catch upticks in temperature or heart rate that might signal that a health care worker had been infected with the virus. In San Diego, Scripps Research Translational Institute scientists are recruiting people with virtually any kind of wearable — from Apple Watches to Fitbits — to try and predict regional clusters of the virus using data on heart rate, temperature, and activity and sleep levels.

Both research groups said they’re pushing to get the research off the ground at an unprecedented pace.

“We’re racing against the clock,” Eric Topol, director of the Scripps Research Translational Institute, told STAT. “The sooner we can recruit and enroll a large number of people, the sooner we’ll have a chance to predict an outbreak.”

Topol envisions the Scripps study functioning somewhat like a Google Maps for health data — but instead of red and green highways signaling traffic patterns, data-driven clusters would warn of the next coronavirus hotspot. To make this happen, large numbers of wearable users — on the order of roughly a million people — will need to participate.

The UCSF researchers want to use wearable data from Oura rings to help predict which health care workers are about to fall ill, so they can be isolated and cared for. Oura is sponsoring the study; a private, undisclosed donor is providing further funding.

“Frontline health care workers are more likely to be exposed than anybody else. So if an algorithm can help predict the onset of symptoms, [we may be able to use it so that in the future], they can take action sooner,” said Ashley Mason, an assistant professor of psychology at the UCSF Osher Center for Integrative Medicine and the principal investigator on the study. Mason hopes to recruit several thousand participants — both health care workers and existing Oura ring users — over the next few weeks.

When someone begins to come down with a viral infection like the seasonal flu, the body often begins responding before the brain is even aware they are ill. Temperature and resting heart rate often rise slightly. As fatigue settles in, activity levels drop and time spent sleeping rises.

“It’s a chance for us to see how your body is changing long before you do; to see how your body is mounting a disease response,” said Benjamin Smarr, assistant professor of bioengineering and data science at the University of California, San Diego, and a researcher involved in the UCSF-Oura study.

The Scripps’ study launched on Wednesday and will last two years. It was inspired by earlier work the institution conducted using Fitbit data to track the seasonal flu. In January, the researchers published a study on that work, which pulled together two years’ worth of de-identified Fitbit data from nearly 50,000 users. The researchers found that wearable data could more accurately predict local flu outbreaks than the standard system used by the Centers for Disease Control and Prevention.

Since coronavirus and the seasonal flu share some symptoms, Topol hopes they’ll be able to pinpoint the start of an outbreak before people start flocking to emergency rooms. Their timing is key.

“This is an outbreak that’s going to go on for 18 months in cycles, but right now is the one that’s wreaking havoc. The sooner we can get on board the better,” said Topol.

The idea for UCSF’s research also came from a previous project. Mason had been gearing up to examine temperature data from Oura rings in people with depression. She was interested in studying whether people with depression — who tend to have higher body temperatures — might be helped by repeatedly exposing themselves to the intense heat of saunas, which spur the body’s sweat response.

With that research on pause during the coronavirus crisis, Mason searched for a way to help. She had the idea to harness temperature data for another purpose: flagging signs of illness among health care workers at the front lines of the crisis.

“The next day we got the ball rolling,” Mason said.

The UCSF study — which launched on Monday and will last three months — will collect ring data on users’ temperature, heart rate, breathing rate, and activity levels. UCSF is currently distributing 2,000 rings to frontline health care workers and has expanded the study to anyone with an Oura ring. Similar to the Scripps study, user data will be de-identified, Mason said.

Both studies also ask participants to check in daily and enter symptoms like coughing or a runny nose.

“We’ve got to get ahead of this outbreak,” Topol said. “It’s obviously gotten ahead of us.”

With countries from Italy to the U.S. having waited too long to combat the coronavirus, many experts in public health and epidemiology are pleading with government officials not to compound the mistake by lifting stay-at-home and other social distancing measures too soon — and, in fact, to impose strict ones in U.S. states and cities that haven’t.

But from the World Health Organization to New York Gov. Andrew Cuomo to epidemiology modelers across the globe, there is growing recognition that the time will and must come to tiptoe back toward normalcy.

That recognition is driving the next life-and-death questions in the coronavirus pandemic: What is the exit strategy? How will we know when it’s safe to implement it? If this first wave of outbreak eventually crests and dissipates, as it has in China, what’s the plan if the virus returns with a vengeance in a few months? Can that plan be less disruptive to livelihoods and ordinary existence than the panicked responses in many western countries over the last month, and more like the surgical strikes that seem to have succeeded in Singapore and South Korea?

The “when can we?” research, unfortunately, is playing out against a highly politicized background. President Trump on Tuesday vowed to return the country to “normal” by Easter, April 12. But while the epidemic in the U.S. is still far from under control, much less peaking, apolitical experts are nevertheless cautiously starting to figure out how smarter, targeted approaches could serve as an off-ramp for the current control measures and how to do better next time, especially if Covid-19 cases rebound after the current outbreak fades.

“You can’t stop the economy forever,” Cuomo — whose state has more Covid-19 cases and stricter restrictions than any other — said in a news conference on Monday. “So we have to start to think about, does everyone stay out of work? Should young people go back to work sooner? Can we test for those who had the virus, resolved, and are now immune and can they start to go back to work?”

He and others who cringe at the very thought of relaxing social distancing, including many infectious disease experts, are asking how to do it right, or at least better. There is reason to hope that will be possible. An emerging consensus points to aggressive tracing of contacts of sick people, much broader testing, targeted quarantines, and new online tracking technology as strategies that would facilitate the easing of social distancing measures.

Scientists including infectious disease epidemiologist Marc Lipsitch of the Harvard T.H. Chan School of Public Health, one of the most forceful voices against easing up prematurely on containment and mitigation, conclude in a new paper that in a best-case scenario, “summertime social distancing can be less frequent.” After that, they explain in an analysis published as a preprint on Tuesday, their mathematical model of how people interact and how infections spread suggests that, if the epidemic returns, “aggressive contact tracing and quarantine – impractical now in many places but more practical once case numbers have been reduced and testing scaled up – could alleviate the need for stringent social distancing to maintain control of the epidemic.”

Authoritative support for the possibility of an exit strategy and more targeted countermeasures against a second wave came on Wednesday. Researchers at Imperial College London, whose earlier model projected apocalyptic levels of Covid-19 deaths across the U.S. and United Kingdom absent near-China-level lockdowns and other forms of social distancing, concluded that in once-frozen cities such as Wuhan, “intermediate levels of local activity can be maintained while avoiding a large outbreak.”

The new data, they wrote, “suggest that after very intense social distancing which resulted in containment, China has successfully exited their stringent social distancing policy.” There are indeed “exiting strategies,” Neil Ferguson and his colleagues conclude, and they “can inform decision making processes for countries once containment is achieved.”

The optimism depends on first controlling the current outbreak, however. In many places, that isn’t even in sight, as many hospitals careen toward collapse and U.S. cases and deaths soar. In a TED video chat on Tuesday, Bill Gates warned that re-opening commerce too soon would be tantamount to “ignor[ing] that pile of bodies over in the corner.”

The point of lockdown measures, WHO Director-General Tedros Adhanom Ghebreyesus said during a briefing Wednesday, “is to enable the more precise and targeted measures that are needed to stop transmission and save lives.”

If today’s stringent measures remain, and people adhere to them better than they have, the curve will not only “flatten” but peter out. In that case, key decisions going forward will focus on how to keep Covid-19 cases to a manageable level during a second outbreak.

The approach getting the most support is one that experts have long doubted could work with a respiratory virus: aggressive case finding, contact tracing, community surveillance, isolation of cases, and quarantining of contacts. Both Singapore and South Korea used that, allowing them to make tactical decisions about schools (mostly open in both countries) and public movement, sparing them from shutting down to the extent that the U.S. and many countries in Europe have.

That suggests an exit strategy for the U.S. “If the case numbers are really low enough, you can do a more Singapore-like or Iceland-like strategy of following individual cases rather than just social distancing,” Lipsitch told reporters on Tuesday. (It’s not clear what “low enough” means, though it would be based in part on hospital capacity.) If public health agencies conduct intense testing, including of people without symptoms, and identify and test their contacts, he said, “you may be able to get away potentially with less social distancing the second time around, because you’re also controlling the individual cases.”

The value of doing so would be enormous, since it could replace the draconian steps that are the only option when chains of viral spread can’t be tracked but that have been financially ruinous, especially to low-wage workers. Although “the feasibility of [widespread testing and contact tracing in the U.S.] remains to be seen and requires a lot of coordination that doesn’t yet exist,” Lipsitch cautioned, there are at least two reasons to think it could be brought into existence: technology and weather.

Earlier this month Health and Human Services Secretary Alex Azar called contact tracing “the basic blocking and tackling” to contain an epidemic. Infectious disease experts have never thought contact tracing could work for respiratory diseases (it isn’t done for flu): It takes so long and these infections move so fast. But in 2020, there’s an app for that.

One called Private Kit: Safe Paths, developed by scientists at the Massachusetts Institute of Technology, would upload data to a privacy-protected site on cases and where they had been. Users who had been in close contact with that person would get a notification and could then isolate themselves for two weeks, slowing viral spread from people without symptoms. In contrast, simply interviewing a single case and identifying that person’s contacts takes an average of 12 hours, said MIT’s Francesco Benedetti. Worse, people can’t remember exactly where they were, let alone what strangers they brushed against or breathed on, two weeks ago.

But the near-instantaneous contact tracing made possible by technology “is one of the most important steps we can take, the infectious disease specialists we worked with tell us,” Benedetti said. “This addresses the need for speed.” The technology should be ready for nationwide use “soon,” he said.

It mimics what Singapore was able to accomplish: banning mass gatherings, yes, but not closing schools, and — crucially — interviewing patients and using security camera footage to identify those they encountered and order them into home quarantine. That severed numerous transmission chains.

In Israel, researchers are testing a similar tool to identify and predict virus hot zones. A smartphone-based questionnaire asks people their age, gender, and location as well as whether they have such Covid-19 symptoms as cough, fatigue, shortness of breath, and diarrhea. Some 320,000 Israelis have filled it out, revealing a significant increase in reported symptoms in places where known patients passed through, said Eran Segal of the Weizmann Institute of Science — an indication that the survey can augment laborious contact tracing by health workers. Israel’s case count reached 2,170 cases on Wednesday.

The tool lets a country (or state or city) “identify, ahead of time, regions of outbreak of the virus,” Segal said. “This will allow health officials to deploy testing in a smarter way, identify those individuals who are infected, and isolate them. It can also allow tightening the lockdown in specific locations but more importantly, relieving the lockdown in other regions where no outbreak is expected.”

That suggests not only an exit strategy but also a next-time strategy, he said. “When we eventually release the population from lockdown, such a tool can be critical in management of the spread of the virus, as it may ahead of time inform us of regions where the outbreak is re-emerging.”

It will take weeks, and maybe months, to refine and deploy tools like these. But we may have that breathing room.

How summertime temperatures will affect the virus remains unknown. But there are reasons for optimism.

Although the research is far from definitive, several studies in China find that higher temperatures do decrease Covid-19 incidence. One, a modeling study posted to the preprint site medRxiv on Tuesday, “confirmed that transmission rate decreased with the increase of temperature, leading to further decrease of infection rate and outbreak scale,” scientists at China Medical University wrote. One reason may be that this coronavirus, like that which caused the SARS epidemic in the early 2000s, can’t survive on surfaces as long in warmer weather.

“Other coronaviruses are seasonal,” said Jeff Shaman of the Mailman School of Public Health at Columbia University. “So we might catch a break here.”

The decision by the U.S. and other countries to close businesses, cancel events, issue stay-at-home orders, and ban large (and now small) gatherings was partly driven by the early mathematical model created by the Imperial College team. That drove policies that prioritize widespread and strict countermeasures rather than more targeted ones.

Now that more experts have dug into the model, they are questioning whether officials drew the right conclusions and, especially, whether economy-crippling policies can be avoided once the first phase of the outbreak passes.

For instance, the Imperial College model does not allow for the possibility of detecting asymptomatic individuals through mass testing or contact tracing, as South Korean did instead of issuing stay-at-home orders. With such mass testing, infected people can be identified even before symptoms appear and can isolate themselves for two weeks.

The critics’ intent is not to slam the highly respected Imperial College team, but to suggest that different assumptions can illuminate the exit strategy and the “next time” strategy.

“The model does not account for important individual-level behavior changes that many people adopt to protect themselves in epidemics,” said epidemiologist and modeler Gerardo Chowell of Georgia State University, including “increased hand washing, staying home if sick, reducing social activities, and wearing a face mask.” He agrees that simple face masks do not keep the virus out very well, but they help keep it in, especially when infected people cough or sneeze or even speak. Widespread use of face masks, as in Japan and other countries in east Asia, would be less disruptive than lockdowns.

Another exit strategy, he and others argue, is targeted intervention. “Factors such as population density, urbanization, environmental factors including temperature and humidity, and connectivity to the rest of the world have been shown to drive transmission rates,” Chowell said. “The intensity of the social distancing interventions have to be implemented in light of the local infectious dynamics,” as does the timing of any easing of restrictions.

The question of timing is, of course, key. “The conservative approach is to wait till there are no new cases in an incubation period,” said Yaneer Bar-Yam of the New England Complex Systems Institute, who uses the science of complex interactions to create mathematical models of epidemics. But once the peak of an outbreak has passed in any region, and if travel restrictions prevent imported cases, “we have every reason to believe [contact tracing and isolation of cases and contacts] can work.”

He, too, sees hope for a more targeted approach soon. “Travel restrictions prevent spreading the disease from areas that have it to those that don’t,” Bar-Yam said, “and enables relaxing restrictions earlier in areas where it has been eradicated. Testing enables rapid isolation of individuals so we don’t have to isolate as many people in order to stop the outbreak.”

More and more modelers are discussing “precision quarantine,” as Momiao Xiong of the University of Texas Health Science Center and colleagues in Shanghai call it, to “slow down and keep people from transmitting the disease.” That could help with both an exit strategy and a next-wave strategy.

“Even in a semi-locked-down state, you can prioritize [for testing and contact tracing] people in grocery stores, banks, delivery, and others who come into contact with a lot of people and are therefore most at risk of being super-spreaders,” said Columbia’s Shaman. They should be tested repeatedly.

There will be “a high proportion of susceptible individuals in the population,” Harvard’s Lipsitch and his colleagues explained in their analysis. That could lead “to an intense epidemic … in the late autumn and winter.”

Even  then, the world will likely not see the end of this coronavirus. Instead, they conclude, it will “circulate seasonally with winter peaks in subsequent years.”

Adozen physicians at the epicenter of Italy’s Covid-19 outbreak issued a plea to the rest of the world on Saturday, going beyond the heartbreaking reports of overwhelmed health care workers there and a seemingly uncontrollable death toll to warn that medical practice during a pandemic may need to be turned on its head — with care delivered to many patients at home.

“Western health care systems have been built around the concept of patient-centered care,” physicians Mirco Nacoti, Luca Longhi, and their colleagues at Papa Giovanni XXIII Hospital in Bergamo urge in a paper published on Saturday in NEJM Catalyst, a new peer-reviewed journal from the New England Journal of Medicine. But a pandemic requires “community-centered care.”

The experience of the Bergamo doctors is crucial for U.S. physicians to understand “because some of the mistakes that happened in Italy can happen here,” said Maurizio Cereda, co-director of the surgical ICU at Penn Medicine and a co-author of the paper. The U.S. medical system is centralized, hospital-focused, and patient-centered, as in most western countries, “and the virus exploits this,” he told STAT.

Although Papa Giovanni XXIII Hospital is a new state-of-the-art facility, its 48 intensive-care beds and other advanced treatment capacity have staggered under the Covid-19 caseload, which passed 4,305 this week.

“We are far beyond the tipping point,” Nacoti and his colleagues write. With 70% of ICU beds reserved for critically ill Covid-19 patients, those beds are being allocated only to those “with a reasonable chance to survive,” as physicians make wrenching triage choices to try to keep alive those who have a chance. “Older patients are not being resuscitated and die alone without appropriate palliative care, while the family is notified over the phone, often by a well-intentioned, exhausted, and emotionally depleted physician with no prior contact,” they report.

Most nearby hospitals in the wealthy region are “nearing collapse while medications, mechanical ventilators, oxygen, and personal protective equipment are not available,” the physicians write.

Other health care in northern Italy has come to a near-halt, they report: The system “struggles to deliver regular services, even pregnancy care and child delivery, while cemeteries are overwhelmed … [V]accination programs are on standby.”

With the outbreak of Covid-19, health care professionals are urging people to regularly refrain from touching their face. Is that too much to ask?

There’s no question it’s easier said than done.

According to a 2015 study in the American Journal of Infection Control, people touch their faces more than 20 times an hour on average. About 44 percent of the time, it involves contact with the eyes, nose, or mouth.

From picking up objects to turning doorknobs, we’re constantly touching surfaces contaminated with pathogens. These pathogens can be picked up by our hands and get into the body through mucous membranes on the face — eyes, nose, and mouth — that act as pathways to the throat and lungs. The coronavirus that causes Covid-19 is believed to be spread mostly by inhaling droplets released when an infected individual coughs or sneezes. But these droplets can also land on surfaces that we touch with our hands.

“Some pathogens can last for about nine days on surfaces, so we are constantly coming in contact with potential pathogens that can cause an infection,” said Jennifer Hanrahan, chief of the division of infectious diseases at the University of Toledo Medical Center.

All of which explains why it makes sense for health officials to recommend that people try to avoid touching their faces. But as anyone who has consciously tried to do so knows, it’s hard.

Touching your face is an act that most people perform without thinking, explained Wendy Wood, provost professor of psychology and business at the University of Southern California.

“Whether it is something intrinsic to our species or a learned behavior, we continue to repeat it even if we intend to or not,” she said.

According to Wood, face touching is a behavior that is triggered for a number of reasons. While some people do it to express their emotions, others touch their face in a discussion to make a point. Over time, they form a habit that continues to get repeated unless it is consciously broken.

Experts say one way to break the cycle is to simply make it more difficult to touch your face.

“If people are to wear gloves and glasses, they are less likely to touch their face,” said Wood.

Previous outbreaks, such as SARS, have shown the importance of washing hands regularly and not touching the face with them.

A study published late last year on hand hygiene and the global spread of disease through air transportation found that if people wash their hands while at the airport, the spread of a pandemic could be curbed by up to 69 percent. The same research group previously found only an estimated 20 percent of people have clean hands while at airports.

Christos Nicolaides, a postdoctoral fellow at MIT and lead author of the study, said little things really could make a difference in restricting the spread of coronavirus, and an increase in the number of people with clean hands would have a significant impact on slowing it.

“Big airports around the world, such as London Heathrow, see thousands of people in a day,” he said. “So small tasks like hand washing can affect the global spread of the virus.”