Monday, March 23, 2020

Broad Scientific Consensus Forming on Infection Defensive Stategy Before Vaccines and Treatments Available

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A beach stroller in the Coney Island neighborhood of Brooklyn on Saturday.
A beach stroller in the Coney Island neighborhood of Brooklyn on Saturday.Credit...Victor J. Blue for The New York Times

The Virus Can Be Stopped, but Only With Harsh Steps, Experts Say

Scientists who have fought pandemics describe difficult measures needed to defend the United States against a fast-moving pathogen.

The New York Times

By Donald G. McNeil Jr.

  • March 22, 2020

Terrifying though the coronavirus may be, it can be turned back. China, South Korea, Singapore and Taiwan have demonstrated that, with furious efforts, the contagion can be brought to heel.

Whether they can keep it suppressed remains to be seen. But for the United States to repeat their successes will take extraordinary levels of coordination and money from the country's leaders, and extraordinary levels of trust and cooperation from citizens. It will also require international partnerships in an interconnected world.

There is a chance to stop the coronavirus. This contagion has a weakness.

Although there are incidents of rampant spread, as happened on the cruise ship Diamond Princess, the coronavirus more often infects clusters of family members, friends and work colleagues, said Dr. David L. Heymann, who chairs an expert panel advising the World Health Organization on emergencies.

No one is certain why the virus travels in this way, but experts see an opening nonetheless. "You can contain clusters," Dr. Heymann said. "You need to identify and stop discrete outbreaks, and then do rigorous contact tracing."

But doing so takes intelligent, rapidly adaptive work by health officials, and near-total cooperation from the populace. Containment becomes realistic only when Americans realize that working together is the only way to protect themselves and their loved ones.

In interviews with a dozen of the world's leading experts on fighting epidemics, there was wide agreement on the steps that must be taken immediately.

Those experts included international public health officials who have fought AIDS, malaria, tuberculosis, flu and Ebola; scientists and epidemiologists; and former health officials who led major American global health programs in both Republican and Democratic administrations.

Americans must be persuaded to stay home, they said, and a system put in place to isolate the infected and care for them outside the home. Travel restrictions should be extended, they said; productions of masks and ventilators must be accelerated, and testing problems must be resolved.

But tactics like forced isolation, school closings and pervasive GPS tracking of patients brought more divided reactions.

It was not at all clear that a nation so fundamentally committed to individual liberty and distrustful of government could learn to adapt to many of these measures, especially those that smack of state compulsion.

"The American way is to look for better outcomes through a voluntary system," said Dr. Luciana Borio, who was director of medical and biodefense preparedness for the National Security Council before it was disbanded in 2018.

"I think you can appeal to people to do the right thing."

In the week since the interviews began, remarkable changes have come over American life. State governments are telling residents they must stay home. Nonessential businesses are being shuttered.

The streets are quieter than they have been in generations, and even friends keep a wary distance. What seemed unthinkable just a week ago is rapidly becoming the new normal.

What follows are the recommendations offered by the experts interviewed by The Times.

Scientists must be heard

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Adm. Tim Ziemer, who led the National Security Council's pandemic response unit until it was disbanded in 2018.Credit...Chris Kleponis/dpa, via Alamy

The White House holds frequent media briefings to describe the administration's progress against the pandemic, often led by President Trump or Vice President Mike Pence, flanked by a rotating cast of officials.

Many experts, some of whom are international civil servants, declined to speak on the record for fear of offending the president. But they were united in the opinion that politicians must step aside and let scientists both lead the effort to contain the virus and explain to Americans what must be done.

Just as generals take the lead in giving daily briefings in wartime — as Gen. Norman Schwarzkopf did during the Persian Gulf war — medical experts should be at the microphone now to explain complex ideas like epidemic curves, social distancing and off-label use of drugs.

The microphone should not even be at the White House, scientists said, so that briefings of historic importance do not dissolve into angry, politically charged exchanges with the press corps, as happened again on Friday.

Instead, leaders must describe the looming crisis and the possible solutions in ways that will win the trust of Americans.

Above all, the experts said, briefings should focus on saving lives and making sure that average wage earners survive the coming hard times — not on the stock market, the tourism industry or the president's health. There is no time left to point fingers and assign blame.

"At this point in the emergency, there's little merit in spending time on what we should have done or who's at fault," said Adm. Tim Ziemer, who was the coordinator of the President's Malaria Initiative from 2006 until early 2017 and led the pandemic response unit on the National Security Council before its disbanding.

"We need to focus on the enemy, and that's the virus."

Stop transmission between cities

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Spring breakers this month in Miami Beach, where there wasn't much social distancing.Credit...Scott McIntyre for The New York Times

The next priority, experts said, is extreme social distancing.

If it were possible to wave a magic wand and make all Americans freeze in place for 14 days while sitting six feet apart, epidemiologists say, the whole epidemic would sputter to a halt.

The virus would die out on every contaminated surface and, because almost everyone shows symptoms within two weeks, it would be evident who was infected. If we had enough tests for every American, even the completely asymptomatic cases could be found and isolated.

The crisis would be over.

Obviously, there is no magic wand, and no 300 million tests. But the goal of lockdowns and social distancing is to approximate such a total freeze.

To attempt that, experts said, travel and human interaction must be reduced to a minimum.

Italy moved incrementally: Officials slowly and reluctantly closed restaurants, churches and museums, and banned weddings and funerals. Nonetheless, the country's death count continues to rise.

The United States is slowly following suit. International flights are all but banned, but not domestic ones. California has ordered all residents to stay at home; New York was to shutter all nonessential businesses on Sunday evening.

But other states have fewer restrictions, and in Florida, for days spring break revelers ignored government requests to clear the beaches.

On Friday, Dr. Anthony S. Fauci, chief medical adviser to the White House Coronavirus Task Force, said he advocated restrictive measures all across the country.

In contrast to the halting steps taken here, China shut down Wuhan — the epicenter of the nation's outbreak — and restricted movement in much of the country on Jan. 23, when the country had a mere 500 cases and 17 deaths.

Its rapid action had an important effect: With the virus mostly isolated in one province, the rest of China was able to save Wuhan.

Even as many cities fought their own smaller outbreaks, they sent 40,000 medical workers into Wuhan, roughly doubling its medical force.

In a vast, largely closed society, it can be difficult to know what is happening on the ground, and there is no guarantee that the virus won't roar back as the Chinese economy restarts.

But the lesson is that relatively unaffected regions of the United States will be needed to help rescue overwhelmed cities like New York and Seattle. Keeping these areas at least somewhat free of the coronavirus means enacting strict measures, and quickly.

Stop transmission within cities

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Police officers enforced stay-at-home rules on Friday at a roadblock in Milan.Credit...Alessandro Grassani for The New York Times

Within cities, there are dangerous hot spots: One restaurant, one gym, one hospital, even one taxi may be more contaminated than many identical others nearby because someone had a coughing fit inside.

Each day's delay in stopping human contact, experts said, creates more hot spots, none of which can be identified until about a week later, when the people infected there start falling ill.

To stop the explosion, municipal activity must be curtailed. Still, some Americans must stay on the job: doctors, nurses, ambulance drivers; police officers and firefighters; the technicians who maintain the electrical grid and gas and phone lines.

The delivery of food and medicine must continue, so that people pinned in their homes suffer nothing worse than boredom. Those essential workers may eventually need permits, and a process for issuing them, if the police are needed to enforce stay-at-home orders, as they have been in China and Italy.

People in lockdown adapt. In Wuhan, apartment complexes submit group orders for food, medicine, diapers and other essentials. Shipments are assembled at grocery warehouses or government pantries and dropped off. In Italy, trapped neighbors serenade one another.

It's an intimidating picture. But the weaker the freeze, the more people die in overburdened hospitals — and the longer it ultimately takes for the economy to restart.

South Korea avoided locking down any city, but only by moving early and with extraordinary speed. In January, the country had four companies making tests, and as of March 9 had tested 210,000 citizens — the equivalent of testing 2.3 million Americans.

As of the same date, fewer than 9,000 Americans had been tested.

Everyone who is infected in South Korea goes into isolation in government shelters, and phones and credit card data are used to trace their prior movements and find their contacts. Where they walked before they fell ill is broadcast to the cellphones of everyone who was nearby.

Anyone even potentially exposed is quarantined at home; a GPS app tells the police if that person goes outside. The fine for doing so is $8,000.

British researchers are trying to develop a similar tracking app, albeit one more palatable to citizens in Western democracies.

Fix the testing mess

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A nasal swab taken last week at a drive-through testing site in Jericho, N.Y.Credit...Johnny Milano for The New York Times

Testing must be done in a coordinated and safe way, experts said. The seriously ill must go first, and the testers must be protected.

In China, those seeking a test must describe their symptoms on a telemedicine website. If a nurse decides a test is warranted, they are directed to one of dozens of "fever clinics" set up far from all other patients.

Personnel in head-to-toe gear check their fevers and question them. Then, ideally, patients are given a rapid flu test and a white blood cell count is taken to rule out influenza and bacterial pneumonia.

Then their lungs are visualized in a CT scanner to look for "ground-glass opacities" that indicate pneumonia and rule out cancer and tuberculosis. Only then are they given a diagnostic test for the coronavirus — and they are told to wait at the testing center.

The results take a minimum of four hours; in the past, if results took overnight, patients were moved to a hotel to wait — sometimes for two to three days, if doctors believed retesting was warranted. It can take several days after an exposure for a test to turn positive.

In the United States, people seeking tests are calling their doctors, who may not have them, or sometimes waiting in traffic jams leading to store parking lots. On Friday, New York City limited testing only to those patients requiring hospitalization, saying the system was being overwhelmed.

Isolate the infected

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An intensive care unit in a 400-bed hospital under construction in Milan.Credit...Alessandro Grassani for The New York Times

As soon as possible, experts said, the United States must develop an alternative to the practice of isolating infected people at home, as it endangers families. In China, 75 to 80 percent of all transmission occurred in family clusters.

That pattern has already repeated itself here. Seven members of a large family in New Jersey were infected; four have already died. After a lawyer in New Rochelle, N.Y., fell ill, his wife, son and daughter all tested positive.

Instead of a policy that advises the infected to remain at home, as the Centers for Disease and Prevention now does, experts said cities should establish facilities where the mildly and moderately ill can recuperate under the care and observation of nurses.

Wuhan created many such centers, called "temporary hospitals," each a cross between a dormitory and a first-aid clinic. They had cots and oxygen tanks, but not the advanced machines used in intensive care units.

American cities now have many spaces that could serve as isolation wards. Already New York is considering turning the Jacob K. Javits Convention Center into a temporary hospital, along with the Westchester Convention Center and two university campuses.

Gov. Ron DeSantis of Florida said on Saturday that state officials were also considering opening isolation wards.

In China, said Dr. Bruce Aylward, leader of the World Health Organization's observer team there, people originally resisted leaving home or seeing their children go into isolation centers with no visiting rights — just as Americans no doubt would.

In China, they came to accept it.

"They realized they were keeping their families safe," he said. "Also, isolation is really lonely. It's psychologically difficult. Here, they were all together with other people in the same boat. They supported each other."

Find the fevers

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Health workers conducted temperature checks at a grocery store in Beijing in February.Credit...Kevin Frayer/Getty Images

Because China, Taiwan and Vietnam were hit by SARS in 2003, and South Korea has grappled with MERS, fever checks during disease outbreaks became routine.

In most cities in affected Asian countries, it is commonplace before entering any bus, train or subway station, office building, theater or even a restaurant to get a temperature check. Washing your hands in chlorinated water is often also required.

"They give you a sticker afterward," said Dr. Heymann, who recently spent a week teaching in Singapore. "I built up quite a collection."

In China, having a fever means a mandatory trip to a fever clinic to check for coronavirus. In the Wuhan area, different cities took different approaches.

Cellphone videos from China show police officers knocking on doors and taking temperatures. In some, people who resist are dragged away by force. The city of Ningbo offered bounties of $1,400 to anyone who turned in a coronavirus sufferer.

The city of Qianjiang, by contrast, offered the same amount of money to any resident who came in voluntarily and tested positive.

Some measures made Western experts queasy. It is difficult to imagine Americans permitting a family member with a fever to be dragged to an isolation ward where visitors are not permitted.

"A lot of people's rights were violated," Dr. Borio said.

Voluntary approaches, like explaining to patients that they will be keeping family and friends safe, are more likely to work in the West, she added.

Trace the contacts

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A contact-tracing drive in Srinagar, in Indian-controlled Kashmir, on Thursday.Credit...Dar Yasin/Associated Press

Finding and testing all the contacts of every positive case is essential, experts said. At the peak of its epidemic, Wuhan had 18,000 people tracking down individuals who had come in contact with the infected.

At the moment, the health departments of some American counties lack the manpower to trace even syphilis or tuberculosis, let alone scores of casual contacts of someone infected with the coronavirus.

Dr. Borio suggested that young Americans could use their social networks to "do their own contact tracing." Social media also is used in Asia, but in different ways.

China's strategy is quite intrusive: To use the subway in some cities, citizens must download an app that rates how great a health risk they are. South Korean apps tell users exactly where infected people have traveled.

When he lectured at a Singapore university, Dr. Heymann said, dozens of students were in the room. But just before he began class, they were photographed to record where everyone sat.

"That way, if someone turns up infected later, you can find out who sat near them," Dr. Heymann said. "That's really clever."

Contacts generally must remain home for 14 days and report their temperatures twice a day.

Make masks ubiquitous

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Ashley White, a health worker in Arlington, Va., donned a mask to conduct coronavirus tests at a drive-through testing center on Thursday.Credit...Erin Schaff/The New York Times

American experts have divided opinions about masks, but those who have worked in Asia see their value.

There is very little data showing that flat surgical masks protect healthy individuals from disease. Nonetheless, Asian countries generally make it mandatory that people wear them. In China, the police even used drones to chase individuals down streets, ordering them to go home and mask up.

The Asian approach is less about data than it is about crowd psychology, experts explained.

All experts agree that the sick must wear masks to keep in their coughs. But if a mask indicates that the wearer is sick, many people will be reluctant to wear one. If everyone is required to wear masks, the sick automatically have one on and there is no stigma attached.

Also, experts emphasized, Americans should be taught to take seriously admonitions to stop shaking hands and hugging. The "W.H.O. elbow bump" may look funny, but it's a legitimate technique for preventing infection.

"In Asia, where they went through SARS, people understand the danger," Dr. Heymann said. "It's instilled in the population that you've got to do the right thing."

Preserve vital services

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City officials held an outdoor meeting to coordinate distribution of food aid at the Palazzo Marino in Milan on Friday.Credit...Alessandro Grassani for The New York Times

Federal intervention is necessary for some vital aspects of life during a pandemic.

Only the federal government can enforce interstate commerce laws to ensure that food, water, electricity, gas, phone lines and other basic needs keep flowing across state lines to cities and suburbs.

Mr. Trump has said he could compel companies to prioritize making ventilators, masks and other needed goods. Some have volunteered; the Hanes underwear company, for example, will use its cotton to make masks for hospital workers.

He also has the military; the Navy is committing two hospital ships to the fight. And Mr. Trump can call up the National Guard. As of Saturday evening, more than 6,500 National Guard members already are assisting in the coronavirus response in 38 states, Puerto Rico and the District of Columbia.

High-level decisions like these must be made quickly, experts said.

"Many Western political leaders are behaving as though they are on a tightrope," said Dr. David Nabarro, a W.H.O. special envoy on Covid-19 and a veteran of fights against SARS, Ebola and cholera.

"But there is no choice. We must do all in our power to fight this," he added. "I sense that most people — and certainly those in business — get it. They would prefer to take the bitter medicine at once and contain outbreaks as they start rather than gamble with uncertainty."

Produce ventilators and oxygen

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An intensive care unit in a hospital in Brescia, Italy.Credit...Claudio Furlan/LaPresse, via Associated Press

The roughly 175,000 ventilators in all American hospitals and the national stockpile are expected to be far fewer than are needed to handle a surge of patients desperate for breath.

The machines pump air and oxygen into the lungs, but they normally cost $25,000 or more each, and neither individual hospitals nor the federal emergency stockpile has ever had enough on hand to handle the number of pneumonia patients that this pandemic is expected to produce.

New York, for example, has found about 6,000 ventilators for purchase around the world, Governor Cuomo said. He estimated the state would need about 30,000.

The manufacturers, including a dozen in the United States, say there is no easy way to ramp up production quickly. But it is possible other manufacturers, including aerospace and automobile companies, could be enlisted to do so.

Ventilators are basically air pumps with motors controlled by circuits that make them act like lungs: the pump pushes air into the patient, then stops so the weight of the chest can push the air back out.

Automobiles and airplanes contain many small pumps, like those for oil, water and air-conditioning fluid, that might be modified to act as basic, stripped-down ventilators. On Sunday, Mr. Trump tweeted that Ford and General Motors had been "given the go-ahead" to produce ventilators.

Providers, meanwhile, are scrambling for alternatives.

Canadian nurses are disseminating a 2006 paper describing how one ventilator can be modified to treat four patients simultaneously. Inventors have proposed combining C-PAP machines, which many apnea sufferers own, and oxygen tanks to improvise a ventilator.

The United States must also work to increase its supply of piped and tanked oxygen, Dr. Aylward said.

One of the lessons of China, he noted, was that many Covid-19 patients who would normally have been intubated and on ventilators managed to survive with oxygen alone.

Retrofit hospitals

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Construction of one of two new hospitals to treat coronavirus patients in Wuhan, China, in January.Credit...Chinatopix, via Associated Press

Hospitals in the United States have taken some measures to handle surges of patients, such as stopping elective surgery and setting up isolation rooms.

To protect bedridden long-term patients, nursing homes and hospitals also should immediately stop admitting visitors and do constant health checks on their staffs, said Dr. James LeDuc, director of the Galveston National Laboratory at the University of Texas Medical Branch.

The national stockpile does contain some prepackaged military field hospitals, but they are not expected to be nearly enough for a big surge.

In Wuhan, the Chinese government famously built two new hospitals in two weeks. All other hospitals were divided: 48 were designated to handle 10,000 serious or critical coronavirus patients, while others were restricted to handling emergencies like heart attacks and births.

Wherever that was impractical, hospitals were divided into "clean" and "dirty" zones, and the medical teams did not cross over. Walls to isolate whole wards were built, and — as in Ebola wards — doctors went in one end of the room wearing protective gear and left by the other end, where they de-gowned under the eyes of a nurse to prevent infection.

Decide when to close schools

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The closed Bear Creek Middle School in Fairburn, Ga.Credit...Melissa Golden for The New York Times

As of Saturday, schools in 45 states were closed entirely, but that is a decision that divided experts.

"Closing all schools may not make sense unless there is documented widespread community transmission, which we're not seeing in most of the country," said Dr. Thomas R. Frieden, a former C.D.C. director under President Barack Obama.

It is unclear how much children spread coronavirus. They very seldom get sick enough to be hospitalized, which is not true of flu. Current testing cannot tell whether most do not even become infected.

In China, Dr. Aylward said, he asked all of the doctors he spoke to whether they had seen any family clusters in which a child was the first to be infected. No one had, he said, which astonished him.

That leaves a quandary. Closing schools is a normal part of social distancing; after all, schools are the workplaces for many adults, too. And when the disease is clearly spreading within an individual school, it must close.

But closing whole school districts can seriously disrupt a city's ability to fight an outbreak. With their children stuck at home, nurses, doctors, police officers and other emergency medical workers cannot come to work.

Also, many children in low-income families depend on the meals they eat at schools.

Cities that close all schools are creating special "hub schools" for the children of essential workers. In Ohio, the governor has told school bus drivers to deliver hot meals to children who normally got them at school.

Recruit volunteers

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Residents received a delivery of food in Wuhan this month.Credit...Agence France-Presse — Getty Images

China's effort succeeded, experts said, in part because of hundreds of thousands of volunteers. The government declared a "people's war" and rolled out a "Fight On, Wuhan! Fight On, China!" campaign.

It made inspirational films that combined airline ads with 1940s-style wartime propaganda. The ads were somewhat corny, but they rallied the public.

Many people idled by the lockdowns stepped up to act as fever checkers, contact tracers, hospital construction workers, food deliverers, even babysitters for the children of first responders, or as crematory workers.

With training, volunteers were able to do some ground-level but crucial medical tasks, such as basic nursing, lab technician work or making sure that hospital rooms were correctly decontaminated.

Americans often step forward to help neighbors affected by hurricanes and floods; many will no doubt do so in this outbreak, but they will need training in how not to fall ill and add to the problem.

"In my experience, success is dependent on how much the public is informed and participates," Admiral Ziemer said. "This truly is an 'all hands on deck' situation."

Prioritize the treatments

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Claire Liu, a postdoctoral student at the Icahn School of Medicine at Mount Sinai Hospital in Manhattan prepared cell samples for experimental infection with the coronavirus.Credit...Victor J. Blue for The New York Times

Clinicians in China, Italy and France have thrown virtually everything they had in hospital pharmacies into the fight, and at least two possibilities have emerged that might save patients: the anti-malaria drugs chloroquine and hydroxychloroquine, and the antiviral remdesivir, which has no licensed use.

There is not proof yet that any of these are effective against the virus. China registered more than 200 clinical trials, including several involving those treatments, but investigators ran out of patients in critical condition to enroll. Italy and France have trials underway, and hospitals in New York are writing trial protocols now.

One worry for trial leaders is that chloroquine has been given so much publicity that patients may refuse to be "randomized" and accept a 50 percent chance of being given a placebo.

If any drug works on critical cases, it might be possible to use small doses as a prophylactic to prevent infection.

An alternative is to harvest protective antibodies from the blood of people who have survived the illness, said Dr. Peter J. Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston.

The purified blood serum — called immunoglobulin — could possibly be used in small amounts to protect emergency medical workers, too.

"Unfortunately, the first wave won't benefit from this," Dr. Hotez said. "We need to wait until we have enough survivors."

Find a vaccine

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Dr. Anthony Fauci, the Trump administration's coronavirus task force infectious disease expert, this month during a White House briefing.Credit...Al Drago for The New York Times

The ultimate hope is to have a vaccine that will protect everyone, and many companies and governments have already rushed the design of candidate vaccines. But as Dr. Fauci has explained multiple times, testing those candidate vaccines for safety and effectiveness takes time.

The process will take at least a year, even if nothing goes wrong. The roadblock, vaccine experts explained, is not bureaucratic. It is that the human immune system takes weeks to produce antibodies, and some dangerous side effects can take weeks to appear.

After extensive animal testing, vaccines are normally given to about 50 healthy human volunteers to see if they cause any unexpected side effects and to measure what dose produces enough antibodies to be considered protective.

If that goes well, the trial enrolls hundreds or thousands of volunteers in an area where the virus is circulating. Half get the vaccine, the rest do not — and the investigators wait. If the vaccinated half do not get the disease, the green light for production is finally given.

In the past, some experimental vaccines have produced serious side effects, like Guillain-Barre syndrome, which can paralyze and kill. A greater danger, experts said, is that some experimental vaccines, paradoxically, cause "immune enhancement," meaning they make it more likely, not less, that recipients will get a disease. That would be a disaster.

One candidate coronavirus vaccine Dr. Hotez invented 10 years ago in the wake of SARS, he said, had to be abandoned when it appeared to make mice more likely to die from pneumonia when they were experimentally infected with the virus.

In theory, the testing process could be sped up with "challenge trials," in which healthy volunteers get the vaccine and then are deliberately infected. But that is ethically fraught when there is no cure for Covid-19. Even some healthy young people have died from this virus.

Reach out to other nations

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Tedros Adhanom Ghebreyesus, director-general of the W.H.O., second from left, at a coronavirus briefing in Geneva in January.Credit...Denis Balibouse/Reuters

Wealthy nations need to remember that, as much as they are struggling with the virus, poorer countries will have a far harder time and need help.

Also, the Asian nations that have contained the virus could offer expertise — and desperately needed equipment. Jack Ma, the billionaire founder of Alibaba, recently offered large shipments of masks and testing kits to the United States.

Wealthy nations ignored the daily warnings from Tedros Adhanom Ghebreyesus, the W.H.O.'s director general, that far more aggressive efforts at isolation and contact tracing were urgently needed to stop the virus.

"Middle income and poorer nations are following the advice of international organizations while the most advanced nations find it so hard to implement it," Dr. Nabarro said. "That must change."

In declaring the coronavirus a pandemic, Dr. Tedros called for countries to learn from one another's successes, act with unity and help protect one another against a threat to people of every nationality.

"Let's all look out for each other," he said.

Donald G. McNeil Jr. is a science reporter covering epidemics and diseases of the world's poor. He joined The Times in 1976, and has reported from 60 countries.  


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