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Several of my colleagues and students and I have statistically analyzed thousands of seasonal coronavirus cases in the United States and used a mathematical model to infer that immunity over a year or so is likely for the two seasonal coronaviruses most closely related to SARS-CoV-2 — an indication perhaps of how immunity to SARS-CoV-2 itself might also behave.

Mild illness, in other words, might not always build up protection. Similarly, it will be important to study the immune responses of people with asymptomatic cases of SARS-CoV-2 infection to determine whether symptoms, and their severity, predict whether a person becomes immune.

the issue might be resolved by comparing the viral genome sequence from the first and the second periods of infection.

it is reasonable to assume that only a minority of the world’s population is immune to SARS-CoV-2, even in hard-hit areas. How could this tentative picture evolve as better data come in? Early hints suggest that it could change in either direction.

One recent study (not yet peer-reviewed) suggests that rather than, say, 10 times the number of detected cases, the United States may really have more like 100, or even 1,000, times the official number

if this one is correct, then herd immunity to SARS-CoV-2 could be building faster than the commonly reported figures suggest.

another recent study (also not yet peer-reviewed) suggests that not every case of infection may be contributing to herd immunity. Of 175 Chinese patients with mild symptoms of Covid-19, 70 percent developed strong antibody responses, but about 25 percent developed a low response and about 5 percent developed no detectable response at all

An alternative possibility, which many scientists think is more likely, is that these patients had a false negative test in the middle of an ongoing infection, or that the infection had temporarily subsided and then re-emerged

The balance between these uncertainties will become clearer when more serologic surveys, or blood tests for antibodies, are conducted on large numbers of people. Such studies are beginning and should show results soon. Of course, much will depend on how sensitive and specific the various tests are: how well they spot SARS-CoV-2 antibodies when those are present and if they can avoid spurious signals from antibodies to related viruses.

Based on the volunteer experiments with seasonal coronaviruses and the antibody-persistence studies for SARS and MERS, one might expect a strong immune response to SARS-CoV-2 to protect completely against reinfection and a weaker one to protect against severe infection and so still slow the virus’s spread.

But designing valid epidemiologic studies to figure all of this out is not easy — many scientists, including several teams of which I’m a part — are working on the issue right now.

getting a handle on this fast is extremely important: not only to estimate the extent of herd immunity, but also to figure out whether some people can re-enter society safely, without becoming infected again or serving as a vector, and spreading the virus to others. Central to this effort will be figuring out how long protection lasts.

Experimental and statistical evidence suggests that infection with one coronavirus can offer some degree of immunity against distinct but related coronaviruses.

then there is the question of immune enhancement: Through a variety of mechanisms, immunity to a coronavirus can in some instances exacerbate an infection rather than prevent or mitigate it.

administering a vaccine against dengue fever, a flavivirus infection, can sometimes make the disease worse.

concern that they might be at play is one of the obstacles that have slowed the development of experimental vaccines against SARS and MERS.

The good news is that research on SARS and MERS has begun to clarify how enhancement works, suggesting ways around it, and an extraordinary range of efforts is underway to find a vaccine for Covid-19, using multiple approaches.

Another diagnostic test under development would work much like an at-home pregnancy test. You would swab your nose, but instead of sending it into a processing center, you’d put it in a liquid and then pour that liquid onto a strip of paper, which would change color if the virus was present. This test may be available in a few months.

We need one other advance in testing, but it’s social, not technical: consistent standards about who can get tested. If the country doesn’t test the right people — essential workers, people who are symptomatic and those who have been in contact with someone who tested positive — then we’re wasting a precious resource and potentially missing big reserves of the virus.

identifying the antibodies that are most effective against the novel coronavirus, and then manufacturing them in a lab. If this works, it is not yet clear how many doses could be produced; it depends on how much antibody material is needed per dose. In 2021, manufacturers may be able to make as few as 100,000 treatments or many millions.

An even better solution would be the broad, voluntary adoption of digital tools. For example, there are apps that will help you remember where you have been

treatment options

giving the plasma (and the antibodies it contains) to sick people. Several major companies are working together to see whether this succeeds.

The second area where we need innovation is contact tracing

Unfortunately, based on the evidence I’ve seen, they’ll likely find a good treatment, but not one that virtually guarantees you’ll recover.

making a vaccine.

The new approach I’m most excited about is known as an RNA vaccine.

an RNA vaccine gives your body the genetic code needed to produce viral fragments on its own.

n RNA vaccine essentially turns your body into its own vaccine manufacturing unit.

World War II was the defining moment of my parents’ generation. Similarly, the coronavirus pandemic — the first in a century — will define this era

here is one big difference between a world war and a pandemic: All of humanity can work together to learn about the disease and develop the capacity to fight it. With the right tools in hand, and smart implementation, we will eventually be able to declare an end to this pandemic

the Russian disinformation effort has proven far harder to track and combat because Russian operatives were taking advantage of Facebook’s core functions, connecting users with shared content and with targeted native ads to shape the political environment in an unusually contentious political season, say people familiar with Facebook’s response.

Unlike the Islamic State, what Russian operatives posted on Facebook was, for the most part, indistinguishable from legitimate political speech. The difference was the accounts that were set up to spread the misinformation and hate were illegitimate.

Facebook’s cyber experts found evidence that members of APT28 were setting up a series of shadowy accounts — including a persona known as Guccifer 2.0 and a Facebook page called DCLeaks — to promote stolen emails and other documents during the presidential race. Facebook officials once again contacted the FBI to share what they had seen.

The sophistication of the Russian tactics caught Facebook off-guard. Its highly regarded security team had erected formidable defenses against traditional cyber attacks but failed to anticipate that Facebook users — deploying easily available automated tools such as ad micro-targeting — pumped skillfully crafted propaganda through the social network without setting off any alarm bells.

One of the theories to emerge from their post-mortem was that Russian operatives who were directed by the Kremlin to support Trump may have taken advantage of Facebook and other social media platforms to direct their messages to American voters in key demographic areas in order to increase enthusiasm for Trump and suppress support for Clinton.

the intelligence agencies had little data on Russia’s use of Facebook and other U.S.-based social media platforms, in part because of rules designed to protect the privacy of communications between Americans.

“It is our responsibility,” he wrote, “to amplify the good effects [of the Facebook platform] and mitigate the bad — to continue increasing diversity while strengthening our common understanding so our community can create the greatest positive impact on the world.”

The extent of Facebook’s internal self-examination became clear in April, when Facebook Chief Security Officer Alex Stamos co-authored a 13-page white paper detailing the results of a sprawling research effort that included input from experts from across the company, who in some cases also worked to build new software aimed specifically at detecting foreign propaganda.

“Facebook sits at a critical juncture,” Stamos wrote in the paper, adding that the effort focused on “actions taken by organized actors (governments or non-state actors) to distort domestic or foreign political sentiment, most frequently to achieve a strategic and/or geopolitical outcome.” He described how the company had used a technique known as machine learning to build specialized data-mining software that can detect patterns of behavior — for example, the repeated posting of the same content — that malevolent actors might use.  

The software tool was given a secret designation, and Facebook is now deploying it and others in the run-up to elections around the world. It was used in the French election in May, where it helped disable 30,000 fake accounts, the company said. It was put to the test again on Sunday when Germans went to the polls. Facebook declined to share the software tool’s code name. 

Officials said Stamos underlined to Warner the magnitude of the challenge Facebook faced policing political content that looked legitimate. Stamos told Warner that Facebook had found no accounts that used advertising but agreed with the senator that some probably existed. The difficulty for Facebook was finding them.

Technicians then searched for “indicators” that would link those ads to Russia. To narrow down the search further, Facebook zeroed in on a Russian entity known as the Internet Research Agency, which had been publicly identified as a troll farm.

By early August, Facebook had identified more than 3,000 ads addressing social and political issues that ran in the United States between 2015 and 2017 and that appear to have come from accounts associated with the Internet Research Agency.

Congressional investigators say the disclosure only scratches the surface. One called Facebook’s discoveries thus far “the tip of the iceberg.” Nobody really knows how many accounts are out there and how to prevent more of them from being created to shape the next election — and turn American society against itself.

The data, aggregated by ZIP code, will also be incorporated into illness signals that Kinsa makes available in its public HealthWeather map. The company sometimes shares this ZIP-code-level information with pharmacies, vaccine distributors and other companies. Clorox, for instance, has used Kinsa’s data to determine where to target its ads. (Lysol will have no special access to the data, Kinsa says.)

And then, of course, there are the inevitable privacy concerns. Kinsa emphasizes that all data provided to the city will be aggregated and anonymized.

City health officials will also have access to this aggregated, anonymized data, which they hope will help them identify unusual illness clusters earlier than is currently possible. “It’s measuring something that we’ve never really been able to measure before,” Dr. Varma said. “This is information about people’s biological measurements, being taken by somebody in their home before they’ve actually, in many situations, sought care.”

Over the coming months, city officials will keep close tabs on how well the program is working, Dr. Varma said.

On Saturday, Britain reported eight cases of one of the variants found in Brazil, hours after the British authorities imposed a travel ban from Latin American countries and Portugal, which is linked to Brazil by its colonial history and by current travel and trade ties. Italy also suspended flights from Brazil, its health minister, Roberto Speranza, announced on Facebook.

Dr. Brannon Traxler, the department's interim public health director, said that the variant's arrival is an important reminder that the fight against COVID-19 is far from over.

Noting the limited supply of vaccines, she added, "Every one of us must recommit to the fight by recognizing that we are all on the front lines now. We are all in this together."

But the one first seen in South Africa has more mutations in its spike protein than the one from the United Kingdom. Several of its mutations are also present in a variant that was first identified in Brazil.

Earlier this week, Moderna said its COVID-19 vaccine offers protection against new variants of the coronavirus — but that the vaccine is more effective against the strain first identified in the U.K. than the one found in South Africa.

The company said that when its vaccine was used against the variant from South Africa, the vaccine produced levels of virus-fighting antibody titers that were around six times less than when it's used against other variants.

As a result, Moderna said it will test booster doses of its vaccine, including one that would be tailored to fight strains that have recently emerged.

The coronavirus variants have alarmed public health experts in recent months, posing a new challenge even as vaccines from Moderna and Pfizer-BioNTech have raised hopes in the fight against the COVID-19 pandemic.

Researchers have found growing evidence that both of the variants circulating in South Africa and Brazil may be capable of evading the body's immune system, heightening the risk of reinfection, as NPR's Michaeleen Doucleff recently reported.

The first U.S. case of the strain from Brazil was identified earlier this week in the Minneapolis metro are

The problem echoes the country’s catastrophic stumbles early in the pandemic, when a lack of testing allowed the virus to spread widely. Currently, only a tiny fraction of all positive coronavirus tests in the United States are forwarded for further sequencing.

t if scientists don’t know what strains are moving through the population, the mutations that matter may pop up undetected.

For months, scientists have been sounding alarms and trying to ramp up genetic sequencing of test samples, but the effort has been plagued by a lack of funding, political will and federal coordination

Centers for Disease Control and Prevention Director Rochelle Walensky said Friday that the government is increasing the level of sequencing nationwide.“We have scaled up surveillance dramatically just in the last 10 days, in fact. But our plans for scaling up surveillance are even more than what we’ve done so far,”

Ultimately, the country needs real-time data — similar to the dashboards now used to track daily cases, hospitalizations and deaths — to track variants and their prevalence across the country

“None of that exists right now. We’re incredibly behind compared to other countries,”

The U.S. effort is so underdeveloped that it’s impossible to say exactly how many virus cases are sequenced daily.

The CDC has warned that the variant found in the United Kingdom — which British scientists said could be up to 70 percent more transmissible — could become dominant in the United States by March.

It also recently contracted with four private companies — Quest, Labcorp, Illumina and Helix — to conduct more sequencing. By mid-February, those contracts should hit full capacity, analyzing 6,000 samples per week, CDC officials said.

Illumina estimates that the country needs to sequence 5 percent of its coronavirus cases to detect a new variant when the variant represents about 0.1 percent to 1.0 percent of the country’s case

However, the United States so far has only sequenced about 0.32 percent of its total cases

the country ranks 38th out of 130 countries reporting whole-genome sequencing data.

The United States has sequenced 84,177 samples out of 25.7 million cases as of Friday, according to a Washington Post analysis. By comparison, the United Kingdom, in ninth place, has sequenced 214,000 genomes — almost 6 percent — of the country’s 3.7 million cases.

Unlike the United States, the U.K. invested in genetic sequencing early on in the pandemic, launching its genomics consortium in March with a $27 million investment and a multimillion-dollar boost late last year.

Even before the emergence of mutations such as the variants first discovered in South Africa and the United Kingdom, U.S. experts had been warning for months about the need for a national standard for genetic surveillance.

In May, the CDC launched a surveillance program for the coronavirus called SPHERES (SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance). But, in practice, the program relied on a haphazard patchwork of academic labs contributing genetic sequencing on a volunteer basis.

A July report by the National Academies of Science said that “poor funding, coordination, and capacity” had led to a “patchy, typically passive, and reactive” U.S. sequencing effort.

he B.1.351 variant has already spread beyond South Africa to neighboring countries, the United States and Britain. Scientists believe one of its mutations may make it harder for antibodies to grab onto the virus and keep it from entering cells.Among scientists’ worries is that the variant first detected in Britain has acquired the same mutation, known as E484K, in some cases.

Because the trial participants in South Africa were relatively young and unlikely to become severely ill, it was impossible for the scientists to determine if the vaccine protected people from hospitalization or death. Immune responses detected in blood samples from vaccinated people suggest it could.

Like many developing countries, South Africa was relying on the relatively cheap and easy-to-store AstraZeneca shot — “the people’s vaccine,” as Ms. Taylor put it — to tamp down new outbreaks. When airport workers rolled vaccine crates out of the belly of an airplane last week, President Cyril Ramaphosa watched from the rain-soaked tarmac.

Given the proven safety of the AstraZeneca vaccine and the hope that it might yet prevent hospitalizations and deaths from the new variant, Professor Venter said that health officials should consider offering it to anyone who wanted it.

The shortfall in testing isn’t just a problem for individual patients and their doctors. It is also holding back large-scale surveys of seemingly healthy populations, in workplaces and elsewhere, and scientific research into fundamental properties of the virus and the disease it causes.

there is an escalating need to test much larger groups repeatedly—to track the spread of the virus as restrictions ease—and to carry out population-based studies that will reveal more about how this virus behaves.

in determining whether an individual is safe to enter a workplace or school on a given morning. Ideally, for the later purposes, tests would be conducted swiftly and at high volume at the places where samples are taken

All have served in one or more leadership roles: as presidents of universities or other academic institutions, as heads of government agencies, as advisers to drug or biotechnology companies, or simply as pioneers and mentors in their field. All have sought solutions to the great medical problems of our time. None of us can recall a crisis as stark as COVID-19.

While the need for greatly expanded testing in the next phase of this pandemic is widely acknowledged, the United States has no coordinated plan for how to achieve it. The technical building blocks are in hand, but how to put them together is not yet clear. Moreover, major regulatory hurdles limit the use of the results from novel tests in patient care, especially in certain states such as New York. And the logistics of deploying enough personnel to track samples and deliver results are daunting. Because of the complexity and importance of such testing, a centralized program, run by a strong scientific leader and paid for with federal dollars, may be the only solution.

rmed with efficient and accurate tests to detect the virus (indicating active infection) and reliable tests to measure antibodies against it (implying prior exposure and possible immunity), public-health programs could paint an accurate picture of the current pandemic. Small and large businesses, schools, health-care facilities, and other organizations could track the outcomes of their attempts to restore normal activities, and scientists could answer key questions about viral transmission and host immunity.

decisive answers will come only from studying human beings who are exposed to the virus under real-life conditions. Such studies may be feasible only under circumstances in which natural transmission is occurring at significant rates, as it currently is. Therefore, if we are to get answers to the following questions, we must act now.

tudies to answer these questions require identifying enough people who have recovered, then testing them repeatedly for the appearance of a new infection. Such people are relatively easy to find. They include doctors and nurses in hospitals in hard-hit metropolitan areas such as New York City; staff and residents at nursing homes with high rates of infection; and crews of U.S. Navy ships that have experienced outbreaks of COVID-19.

identify asymptomatic infections. Following up on those cases will shed light on how many asymptomatic people ultimately develop symptoms; how long it takes for them to do so; whether asymptomatic people who ultimately develop symptoms have higher viral loads than those who don’t get sick; whether symptomatic and asymptomatic people have different immune responses; whether other, simpler procedures (such as tests for some chemical abnormality in the blood) might be used to screen for infection; and how large a contribution asymptomatic people make to the ongoing transmission of the virus.

Despite repeated warnings after prior epidemics about the likelihood of new ones caused by novel microbes, the United States and many other countries failed to respond efficiently to this one. Scientists might have detected the new coronavirus much earlier with the better tools for microbial surveillance that already exist; prevented the pathogen’s worldwide spread by more aggressive testing and contact tracing; and supported better and safer health care with larger stockpiles and pipelines for procurement of medical equipment. Humanity should never be this unprepared again.

Julia Lyons saw an opportunity. Figuring nobody would have time to check her lack of credentials, she signed on at a home-nurse registry under various names. In late 1918, the Tribune chronicled the fake flu nurse’s escapades like a dime detective novel.

The police tapped the phone and learned Julia lived nearby. Detectives trailed Julia. One day she set off to marry Charlie the Greek, who ran the Victory Restaurant on West Madison Avenue. Before vows could be exchanged, Julia was in handcuffs.

Instead of transporting Julia to the courthouse in a patrol wagon, the deputy sheriff took her on a street car. In court, some 50 victims testified against her. She was held under $13,000 bond, the equivalent of more than $190,000 today.Deputy Hickey started back to the county jail with Julia in tow. An hour and a half later he called the police and “excitedly” told them she had jumped from a moving street car and hopped into a waiting automobile. Based on the reported location, one official speculated Hickey and his prisoner had been going to cabarets.

Soon Julia was back at her old tricks. In March 1919, the police traced her through the nurse registry to a home on Fullerton Boulevard. When Julia answered the door, the police nabbed her.

Last year, a Chinese scientist he worked with published a specific forecast: “It is highly likely that future SARS- or MERS-like coronavirus outbreaks will originate from bats, and there is an increased probability that this will occur in China.”

Humans today are exposed to more deadly new pathogens than ever. They typically come from animals, as global travel, trade and economic development, such as meat production and deforestation, push people, livestock and wildlife closer together

Scientists knew infectious disease outbreaks were becoming more common, with 2010 having more than six times the outbreaks of pathogens from animal origins than in 1980, according to data in a study by Brown University researchers.

Yet plenty was left undone, in areas including funding, early-warning systems, the role of the WHO and coordination with China. A big chunk of U.S. funding went toward protecting Americans against a bioterror attack. Government funding for pandemics has come largely in emergency, one-time packages to stop an ongoing outbreak.

She said a better solution would be to fund public health more like national defense, with much more guaranteed money, year in, year out.

“Will there be another human influenza pandemic?” Dr. Webster asked in a paper presented at an NIH meeting in 1995. “The certainty is that there will be.”

Experts including Dr. Webster were particularly concerned about the potential for spillover in southern China, where large, densely populated cities were expanding rapidly into forests and agricultural lands, bringing people into closer contact with animals. Two of the three influenza pandemics of the 20th century are thought to have originated in China.

Dr. Webster and others warned it could re-emerge or mutate into something more contagious. With U.S. funding, he set up an animal influenza surveillance center in Hong Kong. The WHO, which hadn’t planned for pandemics before, started compiling protocols for a large-scale outbreak, including contingency plans for vaccines.

At a dinner back in the U.S., he remembers one guest saying, “Oh, you really needed to have someone in the U.S. to be impacted to really galvanize the government.”

That “drove home the reality in my own mind of globalization,” said Dr. Fukuda. SARS showed that viruses can crisscross the globe by plane in hours, making a local epidemic much more dangerous.

The WHO’s director-general, Gro Harlem Brundtland, publicly criticized China. The government under new leaders reversed course. It implemented draconian quarantines and sanitized cities, including a reported 80 million people enlisted to clean streets in Guangdong.

By May 2003, the number of new SARS cases was dwindling. It infected around 8,000 people world-wide, killing nearly 10%.

After SARS, China expanded epidemiologist training and increased budgets for new laboratories. It started working more closely in public health with the U.S., the world’s leader. The U.S. CDC opened an office in Beijing to share expertise and make sure coverups never happened again. U.S. CDC officials visiting a new China CDC campus planted a friendship tree.

In Washington in 2005, a powerful player started driving U.S. efforts to become more prepared. President George W. Bush had read author John M. Barry’s “The Great Influenza,” a history of the 1918 flu pandemic

Mr. Bush leaned toward the group of 10 or so officials and said, “I want to see a plan,” according to Dr. Venkayya. “He had been asking questions and not getting answers,” recalled Dr. Venkayya, now president of Takeda Pharmaceutical Co. ’s global vaccine business unit. “He wanted people to see this as a national threat.”

Mr. Bush launched the strategy in November, and Congress approved $6.1 billion in one-time funding.

The CDC began exercises enacting pandemic scenarios and expanded research. The government created the Biomedical Advanced Research and Development Authority to fund companies to develop diagnostics, drugs and vaccines.

A team of researchers also dug into archives of the 1918 pandemic to develop guidelines for mitigating the spread when vaccines aren’t available. The tactics included social distancing, canceling large public gatherings and closing schools—steps adopted this year when Covid-19 struck, though at the time they didn’t include wide-scale lockdowns.

A year after the plan was released, a progress report called for more real-time disease surveillance and preparations for a medical surge to care for large numbers of patients, and stressed strong, coordinated federal planning.

A European vaccine makers’ association said its members had spent around $4 billion on pandemic vaccine research and manufacturing adjustments by 2008.

The $6.1 billion Congress appropriated for Mr. Bush’s pandemic plan was spent mostly to make and stockpile medicines and flu vaccines and to train public-health department staff. The money wasn’t renewed. “The reality is that for any leader it’s really hard to maintain a focus on low-probability high-consequence events, particularly in the health arena,” Dr. Venkayya said.

In the U.S., President Barack Obama’s administration put Mr. Bush’s new plan into action for the first time. By mid-June, swine flu, as it was dubbed, had jumped to 74 countries. The WHO officially labeled it a pandemic, despite some evidence suggesting the sickness was pretty mild in most people.

That put in motion a host of measures, including some “sleeping” contracts with pharmaceutical companies to begin vaccine manufacturing—contracts that countries like the United Kingdom had negotiated ahead of time so they wouldn’t have to scramble during an outbreak.

In August, a panel of scientific advisers to Mr. Obama published a scenario in which as many as 120 million Americans, 40% of the population, could be infected that year, and up to 90,000 people could die.

H1N1 turned out to be much milder. Although it eventually infected more than 60 million Americans, it killed less than 13,000. In Europe, fewer than 5,000 deaths were reported.

The WHO came under fire for labeling the outbreak a pandemic too soon. European lawmakers, health professionals and others suggested the organization may have been pressured by the pharmaceutical industry.

France ordered 94 million doses, but had logged only 1,334 serious cases and 312 deaths as of April 2010. It managed to cancel 50 million doses and sell some to other countries, but it was still stuck with a €365 million tab, or about $520 million at the time, and 25 million extra doses.

The WHO had raised scares for SARS, mad-cow disease, bird flu and now swine flu, and it had been wrong each time, said Paul Flynn, a member of the Council of Europe’s Parliamentary Assembly and a British lawmaker, at a 2010 health committee hearing in Strasbourg.

Ultimately, an investigation by the council’s committee accused the WHO and public-health officials of jumping the gun, wasting money, provoking “unjustified fear” among Europeans and creating risks through vaccines and medications that might not have been sufficiently tested.

“I thought you might have uttered a word of regret or an apology,” Mr. Flynn told Dr. Fukuda, who as a representative of the WHO had been called to testify.

Back in Washington, scientist Dennis Carroll, at the U.S. Agency for International Development, was also convinced that flu wasn’t the only major pandemic threat. In early 2008, Dr. Carroll was intrigued by Dr. Daszak’s newly published research that said viruses from wildlife were a growing threat, and would emerge most frequently where development was bringing people closer to animals.

If most of these viruses spilled over to humans in just a few places, including southern China, USAID could more easily fund an early warning system.

“You didn’t have to look everywhere,” he said he realized. “You could target certain places.” He launched a new USAID effort focused on emerging pandemic threats. One program called Predict had funding of about $20 million a year to identify pathogens in wildlife that have the potential to infect people.

Drs. Daszak, Shi and Wang, supported by funds from Predict, the NIH and China, shifted their focus to Yunnan, a relatively wild and mountainous province that borders Myanmar, Laos and Vietnam.

One key discovery: a coronavirus resembling SARS that lab tests showed could infect human cells. It was the first proof that SARS-like coronaviruses circulating in southern China could hop from bats to people. The scientists warned of their findings in a study published in the journal Nature in 2013.

Evidence grew that showed people in the area were being exposed to coronaviruses. One survey turned up hundreds of villagers who said they recently showed symptoms such as trouble breathing and a fever, suggesting a possible viral infection.

Over the next several years, governments in the U.S. and elsewhere found themselves constantly on the defensive from global viral outbreaks. Time and again, preparedness plans proved insufficient. One, which started sickening people in Saudi Arabia and nearby

On a weekend morning in January 2013, more than a dozen senior Obama administration officials met in a basement family room in the suburban home of a senior National Security Council official. They were brainstorming how to help other countries upgrade their epidemic response capabilities, fueled by bagels and coffee. Emerging disease threats were growing, yet more than 80% of the world’s countries hadn’t met a 2012 International Health Regulations deadline to be able to detect and respond to epidemics.

The session led to the Global Health Security Agenda, launched by the U.S., the WHO and about 30 partners in early 2014, to help nations improve their capabilities within five years.

Money was tight. The U.S. was recovering from the 2008-09 financial crisis, and federal funding to help U.S. states and cities prepare and train for health emergencies was declining. Public-health departments had cut thousands of jobs, and outdated data systems weren’t replaced.

“It was a Hail Mary pass,” said Tom Frieden, who was director of the CDC from 2009 to 2017 and a force behind the creation of the GHSA. “We didn’t have any money.”

At the WHO, Dr. Fukuda was in charge of health security. When the Ebola outbreak was found in March 2014, he and his colleagues were already stretched, after budget cuts and amid other crises.

The United Nations created a special Ebola response mission that assumed the role normally played by the WHO. Mr. Obama sent the U.S. military to Liberia, underscoring the inability of international organizations to fully handle the problem.

It took the WHO until August to raise an international alarm about Ebola. By then, the epidemic was raging. It would become the largest Ebola epidemic in history, with at least 28,600 people infected, and more than 11,300 dead in 10 countries. The largest outbreak before that, in Uganda, had involved 425 cases.

Congress passed a $5.4 billion package in supplemental funds over five years, with about $1 billion going to the GHSA. The flood of money, along with aggressive contact tracing and other steps, helped bring the epidemic to a halt, though it took until mid-2016.

Global health experts and authorities called for changes at the WHO to strengthen epidemic response, and it created an emergencies program. The National Security Council warned that globalization and population growth “will lead to more pandemics,” and called for the U.S. to do more.

r. Carroll of USAID, who had visited West Africa during the crisis, and saw some health workers wrap themselves in garbage bags for protection, started conceiving of a Global Virome Project, to detect and sequence all the unknown viral species in mammals and avian populations on the planet.

Billionaire Bill Gates warned in a TED talk that an infectious disease pandemic posed a greater threat to the world than nuclear war, and urged world leaders to invest more in preparing for one. The Bill & Melinda Gates Foundation helped form a new initiative to finance vaccines for emerging infections, the Coalition for Epidemic Preparedness Innovations.

Congress established a permanent Infectious Diseases Rapid Response Fund for the CDC in fiscal 2019, with $50 million for that year and $85 million in fiscal 2020.

In May 2018, John Bolton, then President Trump’s national security adviser, dismantled an NSC unit that had focused on global health security and biodefense, with staff going to other units. The senior director of the unit left.

It pushed emerging disease threats down one level in the NSC hierarchy, making pandemics compete for attention with issues such as North Korea, said Beth Cameron, a previous senior director of the unit. She is now vice president for global biological policy and programs at the Nuclear Threat Initiative.

Deteriorating relations with China reduced Washington’s activities there just as researchers were becoming more certain of the threat from coronaviruses.

Dr. Carroll had earlier been ordered to suspend his emerging pandemic threats program in China.

Dr. Carroll pitched to USAID his Global Virome Project. USAID wasn’t interested, he said. He left USAID last year. A meeting that Dr. Carroll planned for last August with the Chinese CDC and Chinese Academy of Sciences to form a Chinese National Virome Project was postponed due to a bureaucratic hang-up. Plans to meet are now on hold, due to Covid-19.

Chloroquine had produced what he called “spectacular improvements” in the Chinese patients. “It’s excellent news — this is probably the easiest respiratory infection to treat of all,” Raoult said. “The only thing I’ll tell you is, be careful: Soon the pharmacies won’t have any chloroquine left!”

Raoult wrote his first research paper, in 1979, on a tick-borne infection sometimes known as Marseille fever. The disease was also called “benign summer fever,” and more than 50 years of science said it was nonlethal. And yet one of the 41 patients in his data set had died.

Before submitting the paper, Raoult, who was then a young resident, gave it to a supervising professor for review. “And he takes it,” Raoult told me, “he doesn’t show it to me again, and he publishes it — and he’d taken out the death. Because he didn’t know how to make sense of the death.”

Raoult was disgusted, and the incident shaped his philosophy of scientific inquiry. “I learned that the people who wanted to follow the familiar path were prepared to cheat in order to do it,” he said.

In Raoult’s view, French science was a duchy of appearances, connections and self-reverence. “It was people saying” — he mimed the drone of an aristocrat — “ ‘Oh, him, yes, he’s very good.’ And this reputation, you don’t know what it’s based on, but it’s not the truth.”

“He was a ‘follower,’” Raoult said of the professor. “And these ‘followers’ are all cheaters. That’s what I thought. And it’s still what I think.”

He is, fundamentally, a contrarian. In Raoult’s view, little of consequence has been accomplished by researchers who endorse the habitual tools and theories of their age.

“I’ve spent my life being ‘against,’” he told me. “I tell young scientists: ‘You know, you don’t need a brain to agree. All you need is a spinal cord.’” He is thrilled by conflict. It is a matter both of philosophy — the influence, no doubt, of the thinker he refers to admiringly as “master Nietzsche” — and of temperament.

His peers shake their heads at this behavior but grant him a grudging respect. “You can’t knock him down,” said Mark Pallen, a professor of microbial genomics at the University of East Anglia. “In terms of his place in the canon, the sainthood of science, he’s pretty secure there.”

In 1985 and 1986, Raoult worked at the Naval Medical Research Institute in Bethesda, Md., where he discovered the Science Citation Index. The index, a tool that can be used to measure a scientist’s influence on the basis of his or her publication history, was relatively unknown in France. Raoult looked up the researchers reputed to be the best in Marseille. “It was really the emperor wears no clothes,” he said. “These people didn’t publish. There was one who hadn’t written a paper in 10 years.”

In subsequent work, he demonstrated that Marseille fever was indeed fatal in almost precisely one in every 41 cases.

Raoult’s name sits atop several thousand; in each of the past eight years, he has produced more than 100. In 2020, he has already published at least 54.

Like many doctors, Molina viewed Raoult’s study with skepticism, but he was also curious to see if his proposed treatment regimen might in fact work. He tested hydroxychloroquine and azithromycin in 11 of his own patients. “We had severe patients, and we wanted to try something,” Molina told me. Within five days, one had died, and two others had been transferred out of his service to intensive care. In another patient, the treatment was suspended after the onset of cardiac issues, a known side effect of the drugs. Eight of the 10 surviving patients still tested positive for SARS-CoV-2 at the conclusion of the study period

Raoult is reputed to be an indefatigable worker, but he also achieves his extreme rate of publication by attaching his name to nearly every paper that comes out of his institute.

In recent years, Raoult has amused himself, it seems, by staking out tendentious scientific claims, sometimes in territories that are well beyond the scope of his expertise.

He is skeptical, for instance, of the utility of mathematical modeling in the realm of epidemiology.

The same logic has led him to conclude that climate modelers are no more than “soothsayers” for our “scientistic era” and that their dire predictions are mostly just an attempt to expiate our intense but irrational feelings of guilt.

Raoult’s most recent book, “Epidemics: Real Dangers and False Alerts,” was published in late March, by which time the W.H.O. had reported more than 330,000 confirmed cases of Covid-19 worldwide and more than 14,500 deaths. “This anguish over epidemics,” he writes, “is completely untethered from the reality of deaths from infectious diseases.”

Testing had been scheduled to run for two weeks per patient, but after only six days, the results were so favorable that Raoult decided to end the trial and publish

Others might have proceeded with more caution or perhaps waited to confirm these results with a larger, more rigorous trial. Raoult likes to think of himself as a doctor first, however, with a moral obligation to treat his patients that supersedes any desire to produce reliable data.

For decades, Raoult has boasted of his prodigious rates of publication and citation, which, as objective statistics, he considers to be the best measure of his worth as a researcher.

This observation has come to be known as the parachute paradigm: We tend to accept the claim that parachutes reduce injury among people who leap from airplanes, but this effect has never been proved in a randomized study that compares an experimental parachute group to an unlucky parachuteless control.

“If you don’t have something that’s visible in 10 patients, or 30, it’s useless. It’s not of any consequence.” An effective treatment for a potentially lethal infectious disease will be visible to the naked eye.

There is much about Raoult that might make him, and by extension his proposed treatment, appealing to a man like Trump. He is an iconoclast with funny hair; he thinks almost everyone else is stupid, especially those who are typically regarded as smart; he is beloved by the angry and conspiracy-minded; his self-congratulation is more or less unceasing.

Raoult classified Trump’s psychology as that of an “entrepreneur,” by way of contrast with that of a “politician.” “Entrepreneurs are people who know how to decide, who know how to take risks,” he said. “And at a certain point, to decide is to take a risk. Every decision is a risk.”

The French waited far too long, in his estimation, to approve the use of hydroxychloroquine in Covid-19 patients. The authorization came only after Raoult announced in the press that he would continue, “in accordance with the Hippocratic oath” and effectively in defiance of the government, to treat patients with his combination therapy. “I’m convinced that in the end, everyone will be using this treatment,” Raoult told Le Parisien. “It’s just a matter of time before people agree to eat their hats.”

Raoult had already begun assembling data for a larger study, but he dismissed the need for anything particularly vast or lengthy. Like other critics of the R.C.T., he likes to point out that a number of self-evidently useful developments in the realm of human health have never been validated by such rigorous tests.

Raoult’s study had measured only viral load. It offered no data on clinical outcomes, and it was not clear if the patients’ actual symptoms had improved or indeed whether the patients lived or died. At the outset, 26 patients were assigned to receive hydroxychloroquine, six more than the 20 who appeared in the final results.

The six additional patients had been “lost in follow-up,” the authors wrote, “because of early cessation of treatment.” The reasons given were concerning. One patient stopped taking the drug after developing nausea. Three patients had to be transferred out of the institute to intensive care. One patient died. (Another patient elected to leave the hospital before the end of the treatment cycle.)

“So four of the 26 treated patients were actually not recovering at all,” noted Elisabeth Bik, a scientific consultant who wrote a widely circulated blog post on Raoult’s study. She paraphrased the sarcasm circulating on Twitter: “My results always look amazing if I leave out the patients who died.”

The report was also riddled with discrepancies and apparent errors.

This apparent sloppiness was unsurprising to many of those who have tracked Raoult’s work in the past. A prominent French microbiologist told me that, in terms of publication, Raoult’s reputation among scientists has been “long gone” for some time.

Beyond its apparent errors and omissions, the study’s design — its small size, its flawed control, the unrandomized assignment of patients to the treatment and control groups — was widely viewed to render its results meaningless. Fauci repeatedly called its results “anecdotal”;

Large, well-controlled randomized trials are by no means the only way to arrive at useful scientific insights. Their utility is that they enhance statistical signals such that, amid the noise of human variability and random chance, even the faint effect of some new treatment can be detected.

The results of his initial trial have yet to be replicated. “I think what he secretly hopes is that no one will ever be able to show anything,”

The prime statistical hurdle that any proposed treatment for Covid-19 will have to overcome — one that is delicate for even Raoult’s critics to make note of, amid the sorrow and fear of this pandemic — is that the signal is likely to be very faint, because the disease is, in the end, rarely fatal. Nearly everyone survives; an effective treatment will save the life of the one or so patients in every hundred who would not have lived without it.

“Alzheimer’s drugs, obesity drugs, cardiovascular drugs, osteoporosis drugs: Over and over, there have been what looked like positive results that evaporated on closer inspection. After you’ve experienced this a few times, you take the lesson to heart that the only way to be sure about these things is to run sufficiently powered controlled trials. No shortcuts, no gut feelings — just data.”

“I’ve invented 10 or so treatments in my life,” Raoult told me. “Half of them are prescribed all over the world. I’ve never done a double-blind study in my life, never. Never! Never done anything randomized, either.”

“When you tell the story, it’s extremely straightforward, no? It’s subject, verb, complement: You detect a disease; there’s a drug that’s cheap, whose safety we know all about because there’s two billion people who take it; we prescribe it, and it changes what it changes. It might not be a miracle product, but it’s better than doing nothing, no?”

Raoult had by then begun to lose his composure. He accused Lacombe of being a shill for the pharmaceutical industry; his fans sent her death threats. On Twitter, he called Bik, the consultant who wrote critically about the first study, a “witch hunter” and called a study that she tweeted — one of several published in April and May that seemed to suggest that Raoult’s treatment regimen was ineffectual or even harmful — “fake news.” The authors of another such study were accused of “scientific fraud.” “My detractors are children!” Raoult told an interviewer.

It is possible that hydroxychloroquine and azithromycin are an effective treatment for Covid-19. But Raoult’s study showed, at best, that 20 people who would almost certainly have survived without any treatment at all also survived for six days while taking the drugs Raoult prescribed.

In recent weeks, Raoult has in fact tempered his claims about the virtues of his treatment regimen. The published, peer-reviewed version of the final study noted that another two patients had died, bringing the total to 10. Where the earlier version called the drugs “safe and efficient,” they were now described merely as “safe.”

He has shown flickers of what appears to be doubt.

“I don’t trust popularity,” he told the interviewer. “When too many people think you’re wonderful, you should start to wonder.” His initial YouTube video, “Coronavirus: Game Over!” has also been renamed. The new language is more measured, and in place of the exclamation point there now stands a question mark.

That’s because the PCR (or “have-you-got-it”) test is based on detecting genetic material from the virus – on its own it does not reveal whether that virus is active, and infectious, or not.

“In some persons they begin to feel well again and signs and symptoms including fever decrease, but some then go on to develop respiratory distress and must be provided oxygen in hospital,” said David Heymann, professor of infectious disease epidemiology at the London School of Hygiene and Tropical Medicine. “It appears to be a delayed immune response that is more serious in some persons and that reacts to remaining virus in various organs.”

“[We are] at the beginning of describing what may be a complex picture of chronic disease that may ensue from the initial infection – coming and going in relapsing waves, sometimes almost like a kind of chronic fatigue syndrome,” he said. “[These cases] may reflect examples of virus not fully cleared, or alternatively, some kind of damaging post-hoc disturbance to immune or inflammatory function,” he said.

Experts say it is unlikely. “I know some have discussed ‘reactivation’ of virus, but this seems unhelpful and unsupported to me,” said Altmann. “It’s a term that’s borrowed from other viruses, especially the herpes virus family, that can hide in the body in a latent state to reactivate years later. [There is] no evidence of that at all for coronaviruses.”

How long are people with Covid-19 infectious for? A recent study of 60 coronavirus patients in China showed 10 patients tested positive for Covid-19 after discharge from hospital. However, once again, experts say this could be down to the test picking up genetic material from inactive virus, with other studies, including work in South Korea, suggesting those who test positive with Covid-19 after recovering from the disease are not infectious.

“It’s not uncommon to find virus in the nose or throat for up to four weeks after initial infection, but tests to establish whether this is live infectious virus – as opposed to just genetic material detection – are not normally positive for much longer than a week,” said Killingley, adding: “I haven’t come across relapse cases whereby the initial infection acquired weeks ago reignites itself into an infectious case.”

ost scientists say that people who have had Covid-19 gain some immunity to the virus that causes it. What they don’t know is whether that protection lasts a few months, a few years or a lifetime.

The immune system wards off infections by producing antibodies that fight invaders. A range of hereditary and environmental factors, including diet and sleep patterns, typically affect the strength and longevity of those defenses.

Immunity also depends on the pathogen. For example, infection by the virus that causes measles confers lifelong immunity. Others, like the influenza virus, can mutate so rapidly that protective antibodies might not recognize them during a reinfection.

The novel coronavirus mutates more slowly than the influenza virus. That gives researchers hope that any natural immunity, or vaccine, would offer more lasting protection. Even if someone gets sick again, researchers believe a second infection might be milder than the first.

Data are scant, but preliminary research shows antibodies can emerge within days or several weeks of the onset of symptoms. A study involving 34 hospitalized cases in China found that two patients, both in their 80s, produced antibodies within three days of symptom onset. The rest produced them two weeks after symptoms first surfaced.

A group of Chinese researchers reported in March that they had infected four rhesus macaques, allowed them to recover and then tried to reinfect two of them with the same strain of the virus. Neither became sick again.

Then why are some people testing positive again? South Korean health officials are refraining from labeling them as “reinfections.” Korean doctors involved in a continuing government review believe that those patients likely harbored low levels of the virus that diagnostic polymerase chain reaction, or PCR, tests failed to pick up. In later stages of the disease, the virus settles into the lungs where it can elude detection. The virus, they say, hadn’t been fully cleared from the body.

ow do I know I’ve fully recovered? Clinicians have mixed views on what constitutes recovery because long-term data aren’t yet available. Guidelines vary across the globe, and even within countries. In a peer-reviewed study published last month, researchers in Hong Kong detected the virus in the feces of Covid-19 survivors even as their respiratory samples tested negative. Viral fragments can linger in the body after symptoms disappear, but it doesn’t mean that a person is infectious, or that the disease will make a comeback.

Chinese scientists have even submitted a paper for publication to the Lancet – although it has not yet been peer-reviewed – that claims “Wuhan is not the place where human-to-human Sars-CoV-2 transmission first happened”, suggesting instead that the first case may have been in the “Indian subcontinent”.

Claims that the virus had origins outside China are given little credence by western scientists. Michael Ryan, director of the health emergencies programme at the World Health Organization (WHO), said last week that it would be “highly speculative” to argue that the disease did not emerge in China. “It is clear from a public health perspective that you start your investigations where the human cases first emerged,” he told a news briefing in Geneva.

Reports of Covid circulating in Italy in autumn 2019, based on samples from a cancer unit, seem “weak”, said Prof Jonathan Stoye, a virologist at the Francis Crick Institute in London. “The serological data [from Italy] can most likely be explained by cross-reactive antibodies directed against other coronaviruses.” In other words, antibodies found in the cases in Italy had been triggered in individuals who had been infected by different coronaviruses, not those responsible for Covid-19

And while traces of coronavirus have been found on frozen food packaging, scientists think that represents a very low risk for a disease now believed to be overwhelmingly transmitted through respiratory droplets.

A positive test “doesn’t indicate infectious virus, just that some signal from the virus is present on that surface,” Andrew Pekosz of the Bloomberg School of Public Health at Johns Hopkins University told AP. “I’ve seen no convincing data that Sars-CoV-2 on food packaging poses a significant risk for infection.”

But as the human and economic toll of the pandemic mounts, Beijing is keen to protect its reputation at home and abroad. Covid-19 has now infected over 60 million people and killed nearly 1.5 million.

“China is still struggling to deal with the fact that it is held responsible for the “original sin” of the outbreak, which undercuts virtually every effort to salvage its image,” said Andrew Small, a China scholar and senior fellow with the German Marshall Fund, a US thinktank.

“Recent months have shown what a catastrophic impact the pandemic has had for China in international public opinion.”

He does not think there is any doubt in the minds of senior Chinese leadership about the origin of the virus, and sees the focus on reporting possible alternative origins as a propaganda campaign.

The reports fit an internal narrative of a strong China led by an efficient Communist party. Domestically, Beijing has promoted its enormous success in virtually eradicating the disease and returning life within its borders to something like normal

Internationally, China’s aims probably include introducing some doubt for global audiences who are likely to believe it, turning basic facts into a “contested, politically sensitive matter” in relations with Beijing, Small said.

China’s questioning of the origin of the virus in Wuhan might be more credible if it was supporting an independent investigation into the disease, but instead authorities have repeatedly proved obstructive

WHO investigators who visited Wuhan earlier this year were not able to visit the food market linked to the initial outbreak. A new team is expected to head to China soon to build on initial work by a Chinese team, but they still don’t have a date for travel, with the WHO saying only that they will travel “in due time”.

It is past time for the nation to make the investments we need to prevent, detect and respond quickly to emerging infectious diseases, like the coronavirus, before they sicken Americans and force catastrophic economic shutdowns.

authorities are too often flying blind, uncertain of the trajectory of the disease, slow to identify hot spots and unable to stop the spread of the virus through targeted measures that do not require shutting down entire communities and economies.

The success of public health measures like contact tracing, mask-wearing, and social distancing depends on individuals and communities trusting and adhering to advice from medical professionals and scientists, sometimes delivered by elected and other officials

That public trust must be earned and sustained.

Elected US officials, including the President, often have fallen short as communicators in this pandemic.

The pandemic has taken a grievous toll on the elderly and nursing home residents specifically. It has also hit essential workers hard, and Black, Latino, Native and low-income Americans suffer disproportionately. As of the end of September, according to the Atlantic, Black Americans have died from Covid-19 at 2.3 times the rate of White Americans, comprising 21% of all US deaths from the disease

US government authorities at all levels should target public health investments to increase the resilience of these communities, including universal paid sick leave in declared pandemics, accessible and free testing, and workplace protections and personal protective equipment for essential workers. Social justice and equity in our existing health care system is not just a moral mandate -- it is a matter of basic pandemic preparedness.

The smarter choice is to reform and strengthen the WHO as an essential cornerstone of global pandemic preparedness

The coronavirus demonstrates that an international framework for pandemic detection and response that relies so heavily on the transparency, judgment and discretion of individual national governments leaves too many opportunities for failure.

Alerts from that network should, in turn, notify national public health agencies and the WHO -- and trigger an international response.

Finally, the next president must resist the siren song of vaccine nationalism

So far, the US has chosen not to join COVAX, a groundbreaking consortium of more than 150 countries created not only to develop a vaccine but to ensure that when one emerges it is shared equitably, rather than hoarded by individual countries. We hope that the next president -- whoever he may be -- will reconsider this decision.

When it comes to pandemics, we all sink or swim together,