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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.

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 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One recent study (not yet peer-reviewed) suggests that rather than, say, 10 times the number of detected cases, the United States may really have more like 100, or even 1,000, times the official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another recent study (also not yet peer-reviewed) suggests that not every case of infection may be contributing to herd immunity.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

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 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.

Dr. Shi’s group was fascinated by how coronaviruses jump from species to species. To find viruses, they took samples from bats and other animals, as well as from sick people living near animals carrying these viruses or associated with the wildlife trade. Much of this work was conducted in partnership with the EcoHealth Alliance, a U.S.-based scientific organization that, since 2002, has been awarded over $80 million in federal funding to research the risks of emerging infectious diseases.

Their research showed that the viruses most similar to SARS‑CoV‑2, the virus that caused the pandemic, circulate in bats that live roughly 1,000 miles away from Wuhan. Scientists from Dr. Shi’s team traveled repeatedly to Yunnan province to collect these viruses and had expanded their search to Southeast Asia. Bats in other parts of China have not been found to carry viruses that are as closely related to SARS-CoV-2.

When the Covid-19 outbreak was detected, Dr. Shi initially wondered if the novel coronavirus had come from her laboratory, saying she had never expected such an outbreak to occur in Wuhan.

The SARS‑CoV‑2 virus is exceptionally contagious and can jump from species to species like wildfire. Yet it left no known trace of infection at its source or anywhere along what would have been a thousand-mile journey before emerging in Wuhan.

The year before the outbreak, the Wuhan institute, working with U.S. partners, had proposed creating viruses with SARS‑CoV‑2’s defining feature

The laboratory pursued risky research that resulted in viruses becoming more infectious: Coronaviruses were grown from samples from infected animals and genetically reconstructed and recombined to create new viruses unknown in nature. These new viruses were passed through cells from bats, pigs, primates and humans and were used to infect civets and humanized mice (mice modified with human genes). In essence, this process forced these viruses to adapt to new host species, and the viruses with mutations that allowed them to thrive emerged as victors.

Worse still, as the pandemic raged, their American collaborators failed to publicly reveal the existence of the Defuse proposal. The president of EcoHealth, Peter Daszak, recently admitted to Congress that he doesn’t know about virus samples collected by the Wuhan institute after 2015 and never asked the lab’s scientists if they had started the work described in Defuse.

By 2019, Dr. Shi’s group had published a database describing more than 22,000 collected wildlife samples. But external access was shut off in the fall of 2019, and the database was not shared with American collaborators even after the pandemic started, when such a rich virus collection would have been most useful in tracking the origin of SARS‑CoV‑2. It remains unclear whether the Wuhan institute possessed a precursor of the pandemic virus.

In 2021, The Intercept published a leaked 2018 grant proposal for a research project named Defuse, which had been written as a collaboration between EcoHealth, the Wuhan institute and Ralph Baric at the University of North Carolina, who had been on the cutting edge of coronavirus research for years. The proposal described plans to create viruses strikingly similar to SARS‑CoV‑2.

Coronaviruses bear their name because their surface is studded with protein spikes, like a spiky crown, which they use to enter animal cells. The Defuse project proposed to search for and create SARS-like viruses carrying spikes with a unique feature: a furin cleavage site — the same feature that enhances SARS‑CoV‑2’s infectiousness in humans, making it capable of causing a pandemic. Defuse was never funded by the United States.

owever, in his testimony on Monday, Dr. Fauci explained that the Wuhan institute would not need to rely on U.S. funding to pursue research independently.

While it’s possible that the furin cleavage site could have evolved naturally (as seen in some distantly related coronaviruses), out of the hundreds of SARS-like viruses cataloged by scientists, SARS‑CoV‑2 is the only one known to possess a furin cleavage site in its spike. And the genetic data suggest that the virus had only recently gained the furin cleavage site before it started the pandemic.

Ultimately, a never-before-seen SARS-like virus with a newly introduced furin cleavage site, matching the description in the Wuhan institute’s Defuse proposal, caused an outbreak in Wuhan less than two years after the proposal was drafted.

When the Wuhan scientists published their seminal paper about Covid-19 as the pandemic roared to life in 2020, they did not mention the virus’s furin cleavage site — a feature they should have been on the lookout for, according to their own grant proposal, and a feature quickly recognized by other scientists.

At the Wuhan Institute of Virology, a team of scientists had been hunting for SARS-like viruses for over a decade, led by Shi Zhengl

In May, citing failures in EcoHealth’s monitoring of risky experiments conducted at the Wuhan lab, the Biden administration suspended all federal funding for the organization and Dr. Daszak, and initiated proceedings to bar them from receiving future grants. In his testimony on Monday, Dr. Fauci said that he supported the decision to suspend and bar EcoHealth.

Separately, Dr. Baric described the competitive dynamic between his research group and the institute when he told Congress that the Wuhan scientists would probably not have shared their most interesting newly discovered viruses with him. Documents and email correspondence between the institute and Dr. Baric are still being withheld from the public while their release is fiercely contested in litigation.

In the end, American partners very likely knew of only a fraction of the research done in Wuhan. According to U.S. intelligence sources, some of the institute’s virus research was classified or conducted with or on behalf of the Chinese military.

In the congressional hearing on Monday, Dr. Fauci repeatedly acknowledged the lack of visibility into experiments conducted at the Wuhan institute, saying, “None of us can know everything that’s going on in China, or in Wuhan, or what have you. And that’s the reason why — I say today, and I’ve said at the T.I.,” referring to his transcribed interview with the subcommittee, “I keep an open mind as to what the origin is.”

The Wuhan lab pursued this type of work under low biosafety conditions that could not have contained an airborne virus as infectious as SARS‑CoV‑2.

Labs working with live viruses generally operate at one of four biosafety levels (known in ascending order of stringency as BSL-1, 2, 3 and 4) that describe the work practices that are considered sufficiently safe depending on the characteristics of each pathogen. The Wuhan institute’s scientists worked with SARS-like viruses under inappropriately low biosafety conditions.

​​Biosafety levels are not internationally standardized, and some countries use more permissive protocols than others.

In one experiment, Dr. Shi’s group genetically engineered an unexpectedly deadly SARS-like virus (not closely related to SARS‑CoV‑2) that exhibited a 10,000-fold increase in the quantity of virus in the lungs and brains of humanized mice. Wuhan institute scientists handled these live viruses at low biosafety levels, including BSL-2.

Even the much more stringent containment at BSL-3 cannot fully prevent SARS‑CoV‑2 from escaping. Two years into the pandemic, the virus infected a scientist in a BSL-3 laboratory in Taiwan, which was, at the time, a zero-Covid country. The scientist had been vaccinated and was tested only after losing the sense of smell. By then, more than 100 close contacts had been exposed. Human error is a source of exposure even at the highest biosafety levels, and the risks are much greater for scientists working with infectious pathogens at low biosafety.

An early draft of the Defuse proposal stated that the Wuhan lab would do their virus work at BSL-2 to make it “highly cost-effective.” Dr. Baric added a note to the draft highlighting the importance of using BSL-3 to contain SARS-like viruses that could infect human cells, writing that “U.S. researchers will likely freak out.”

Years later, after SARS‑CoV‑2 had killed millions, Dr. Baric wrote to Dr. Daszak: “I have no doubt that they followed state determined rules and did the work under BSL-2. Yes China has the right to set their own policy. You believe this was appropriate containment if you want but don’t expect me to believe it. Moreover, don’t insult my intelligence by trying to feed me this load of BS.”

SARS‑CoV‑2 is a stealthy virus that transmits effectively through the air, causes a range of symptoms similar to those of other common respiratory diseases and can be spread by infected people before symptoms even appear. If the virus had escaped from a BSL-2 laboratory in 2019, the leak most likely would have gone undetected until too late.

One alarming detail — leaked to The Wall Street Journal and confirmed by current and former U.S. government officials — is that scientists on Dr. Shi’s team fell ill with Covid-like symptoms in the fall of 2019. One of the scientists had been named in the Defuse proposal as the person in charge of virus discovery work. The scientists denied having been sick.

The hypothesis that Covid-19 came from an animal at the Huanan Seafood Market in Wuhan is not supported by strong evidence.

In December 2019, Chinese investigators assumed the outbreak had started at a centrally located market frequented by thousands of visitors daily. This bias in their search for early cases meant that cases unlinked to or located far away from the market would very likely have been missed

To make things worse, the Chinese authorities blocked the reporting of early cases not linked to the market and, claiming biosafety precautions, ordered the destruction of patient samples on January 3, 2020, making it nearly impossible to see the complete picture of the earliest Covid-19 cases. Information about dozens of early cases from November and December 2019 remains inaccessible.

A pair of papers published in Science in 2022 made the best case for SARS‑CoV‑2 having emerged naturally from human-animal contact at the Wuhan market by focusing on a map of the early cases and asserting that the virus had jumped from animals into humans twice at the market in 2019

More recently, the two papers have been countered by other virologists and scientists who convincingly demonstrate that the available market evidence does not distinguish between a human superspreader event and a natural spillover at the market.

Furthermore, the existing genetic and early case data show that all known Covid-19 cases probably stem from a single introduction of SARS‑CoV‑2 into people, and the outbreak at the Wuhan market probably happened after the virus had already been circulating in humans.

Not a single infected animal has ever been confirmed at the market or in its supply chain. Without good evidence that the pandemic started at the Huanan Seafood Market, the fact that the virus emerged in Wuhan points squarely at its unique SARS-like virus laboratory.

With today’s technology, scientists can detect how respiratory viruses — including SARS, MERS and the flu — circulate in animals while making repeated attempts to jump across species. Thankfully, these variants usually fail to transmit well after crossing over to a new species and tend to die off after a small number of infections

investigators have not reported finding any animals infected with SARS‑CoV‑2 that had not been infected by humans. Yet, infected animal sources and other connective pieces of evidence were found for the earlier SARS and MERS outbreaks as quickly as within a few days, despite the less advanced viral forensic technologies of two decades ago.

Even though Wuhan is the home base of virus hunters with world-leading expertise in tracking novel SARS-like viruses, investigators have either failed to collect or report key evidence that would be expected if Covid-19 emerged from the wildlife trade. For example, investigators have not determined that the earliest known cases had exposure to intermediate host animals before falling ill.

No antibody evidence shows that animal traders in Wuhan are regularly exposed to SARS-like viruses, as would be expected in such situations.

In previous outbreaks of coronaviruses, scientists were able to demonstrate natural origin by collecting multiple pieces of evidence linking infected humans to infected animals

In contrast, virologists and other scientists agree that SARS‑CoV‑2 required little to no adaptation to spread rapidly in humans and other animals. The virus appears to have succeeded in causing a pandemic upon its only detected jump into humans.

it was a SARS-like coronavirus with a unique furin cleavage site that emerged in Wuhan, less than two years after scientists, sometimes working under inadequate biosafety conditions, proposed collecting and creating viruses of that same design.

a laboratory accident is the most parsimonious explanation of how the pandemic began.

Given what we now know, investigators should follow their strongest leads and subpoena all exchanges between the Wuhan scientists and their international partners, including unpublished research proposals, manuscripts, data and commercial orders. In particular, exchanges from 2018 and 2019 — the critical two years before the emergence of Covid-19 — are very likely to be illuminating (and require no cooperation from the Chinese government to acquire), yet they remain beyond the public’s view more than four years after the pandemic began.

it is undeniable that U.S. federal funding helped to build an unprecedented collection of SARS-like viruses at the Wuhan institute, as well as contributing to research that enhanced them.

Advocates and funders of the institute’s research, including Dr. Fauci, should cooperate with the investigation to help identify and close the loopholes that allowed such dangerous work to occur. The world must not continue to bear the intolerable risks of research with the potential to cause pandemics.

A successful investigation of the pandemic’s root cause would have the power to break a decades-long scientific impasse on pathogen research safety, determining how governments will spend billions of dollars to prevent future pandemics. A credible investigation would also deter future acts of negligence and deceit by demonstrating that it is indeed possible to be held accountable for causing a viral pandemic

Last but not least, people of all nations need to see their leaders — and especially, their scientists — heading the charge to find out what caused this world-shaking event. Restoring public trust in science and government leadership requires it.

The group’s reopening recommendations include widespread testing, contact tracing and isolation of people who are infected or exposed.

One important factor in transmission is that seemingly benign activities like speaking and breathing produce respiratory bits of varying sizes that can disperse along air currents and potentially infect people nearby.

Health agencies have so far identified respiratory-droplet contact as the major mode of Covid-19 transmission. These large fluid droplets can transfer virus from one person to another if they land on the eyes, nose or mouth. But they tend to fall to the ground or on other surfaces pretty quickly.

Proper ventilation—such as forcing air toward the ceiling and pumping it outside, or bringing fresh air into a room—dilutes the amount of virus in a space, lowering the risk of infection.

The so-called attack rate—the percentage of people who were infected in a specific place or time

that is only a rule of thumb, he cautioned. It could take much less time with a sneeze in the face or other intimate contact where a lot of respiratory droplets are emitted, he said.

When singing, people can emit many large and small respiratory particles. Singers also breathe deeply, increasing the chance they will inhale infectious particles.

Similar transmission dynamics could be at play in other settings where heavy breathing and loud talking are common over extended periods, like gyms, musical or theater performances, conferences, weddings and birthday parties.

An estimated 10% of people with Covid-19 are responsible for about 80% of transmissions, according to a study published recently in Wellcome Open Research. Some people with the virus may have a higher viral load, or produce more droplets when they breathe or speak, or be in a confined space with many people and bad ventilation when they’re at their most infectious point in their illness

additional protocols to interrupt spread, like social distancing in workspaces and providing N95 respirators or other personal protective equipment, might be necessary as well, she said.

overall, “the risk of a given infected person transmitting to people is pretty low,” said Scott Dowell, a deputy director overseeing the Bill & Melinda Gates Foundation’s Covid-19 response. “For every superspreading event you have a lot of times when nobody gets infected.”

The attack rate for Covid-19 in households ranges between 4.6% and 19.3%, according to several studies. It was higher for spouses, at 27.8%, than for other household members, at 17.3%, in one study in China.

The 37-year-old stay-at-home mother was hospitalized with a stroke on April 18 that her doctors attributed to Covid-19, and was still coughing when she went home two days later.

She pushed to get home quickly, she said, because her 4-year-old son has autism and needed her. She kept her distance from family members, covered her mouth when coughing and washed her hands frequently. No one else in the apartment has fallen ill, she said. “Nobody went near me when I was sick,” she said.

Being outside is generally safer, experts say, because viral particles dilute more quickly. But small and large droplets pose a risk even outdoors, when people are in close, prolonged contac

No one knows for sure how much virus it takes for someone to become infected, but recent studies offer some clues

In one small study published recently in the journal Nature, researchers were unable to culture live coronavirus if a patient’s throat swab or milliliter of sputum contained less than one million copies of viral RNA.

“Based on our experiment, I would assume that something above that number would be required for infectivity,” said Clemens Wendtner, one of the study’s lead authors

He and his colleagues found samples from contagious patients with virus levels up to 1,000 times that, which could help explain why the virus is so infectious in the right conditions: It may take much lower levels of virus than what’s found in a sick patient to infect someone else.

Current CDC workplace guidelines don’t talk about distribution of aerosols, or small particles, in a room, said Lisa Brosseau, a respiratory-protection consultan

Another factor is prolonged exposure. That’s generally defined as 15 minutes or more of unprotected contact with someone less than 6 feet away

Some scientists say while aerosol transmission does occur, it doesn’t explain most infections. In addition, the virus doesn’t appear to spread widely through the air.

“If this were transmitted mainly like measles or tuberculosis, where infectious virus lingered in the airspace for a long time, or spread across large airspaces or through air-handling systems, I think you would be seeing a lot more people infected,” said the CDC’s Dr. Brooks.

High-touch surfaces like doorknobs are a risk, but the virus degrades quickly so other surfaces like cardboard boxes are less worrisome,

But I do think it’s going to be a while before this virus becomes completely normal. And I’ve never been convinced that this current generation of elderly people will ever get to a place where it is completely normal. If you’re 65 or 75 or even older — it’s really hard to teach an immune system new tricks if you’re that age

And so while we may see excess mortality in the elderly decline somewhat, I don’t think we’ll see it ever disappear for this generation who was already old when the pandemic hit. Many will never develop that robust, long-term immunological memory we would want to see — and which happens naturally to someone who’s been exposed hundreds of times since they were a little baby.

There’s a similar story with measles. There is no routine later-life sequelae, like shingles, for measles. But what we do see is that, in measles outbreaks today, there are some people who were vaccinated who get it anyway. Maybe 5 to 15 percent of cases are not immunologically naïve people, but vaccinated people.

Is it really the case that, as babies, we are fighting off those viruses hundreds of times?The short answer is yeah. We start seeing viruses when we’re 2 months old, when we’re a month old. And a lot of these viruses we’ve seen literally tens, if not hundreds of times for some people by the time we’re adults. People tend to think that immunity is binary — you’re either immune or you’re not. That couldn’t be farther from the truth. It’s a gradient, and your protection gets stronger the more times you see a virus.

We used to think we just had this spectacular immune response when we first encountered the virus at, say, age 6, and that the immune response lasted until we were 70. But actually what we were seeing was the effect of an immune system being retrained every time it came into contact with the virus after the initial infection — at 6, and 7, and 8, and so on. Every time your friend got chickenpox, or your neighbor, you got a massive boost. You were re-upping your immune response and diversifying your immunological tools — potentially multiple times a year, a kind of natural booster.

But now, in America, kids get chickenpox vaccines. So you don’t have kids in America getting chickenpox today, and never will. But that means that older Americans, who did get it as kids, are not being exposed again — certainly not multiple times each year. And it turns out that, in the absence of routine re-exposures, that first exposure alone isn’t nearly as good at driving lifelong immunity and warding off shingles until your immune system begins to fall apart in old age — it can last until you’re in your 30s, for example but not until your 70s.

With Covid, when it infects you, it can land in your upper respiratory tract and it just start replicating right there. Immediately, it’s present and replicating in your lungs and in your nose. And that alone elicits enough of an immune response to cause us to feel really crappy and even cause us to feel disease.

But we could have just set the narrative better at the beginning: Look, you might get sick again, but your risk of landing in the hospital is going to be really low, and if you get a booster, you might still get sick again, but your risk of landing in the hospital is going to be even lower. That’s something I think humans can deal with, and I think the public could have understood it.

But it’s why we don’t see the severe disease as much, with a second exposure or an exposure after vaccination: For most people, it’s not getting into the heart and the liver and stuff nearly as easily.

But it doesn’t have to. It’s still causing symptomatic disease. And maybe mucosal vaccines could stop this, but without them we’re likely to continue seeing infections and even symptomatic infections.

through most of 2020 and into 2021, though. Back then, I think the conventional wisdom was that a single exposure — through infection or vaccination — would be the end of the pandemic for you. If this is basic virology and immunology, how did we get that so wrong?

The short answer is that epidemiologists are not immunologists and immunologists are not virologists and virologists are not epidemiologists. And, in general, physicians don’t know anything about the details.

But this failure had some pretty concrete impacts. When reinfections first began popping up, people were surprised, they were scared, and then, to some degree, they lost trust in vaccines. And the people they were turning to for guidance — not only did they not warn us about that, they were slow to acknowledge it, as well.

It had dramatic impacts and ripple effects that will last for years to limit our ability to get populations properly vaccinated.

the worst thing we can do during a pandemic is set inappropriately high expectations. These vaccines are incredible, they’ve had an enormously positive impact on mortality, but they were never going to end the pandemic.

And now, there’s a huge number of people questioning, do these vaccines even do anything?

For babies born today, though, I really think they’re not going to view Covid as any different than other viruses. By the time they are 20, it will be like any other virus to them. Because their immune systems will have grown up with it.

Instead, we set society up for failure, since people feel like the government failed everyone, that biology failed us, and that this was a crazy virus that has broken all the rules of our immune system, when it’s just doing what we’ve always known it would do.

How do you wish we had messaged things differently? What would it have meant to communicate early and clearly that Covid was a textbook virus, as you say?I think the biggest thing would have been just to say, we understand the enemy.

To say that this is a textbook virus, it doesn’t mean that it’s not killing people. Objectively, it’s still killing more people than any other infectious disease

What it means is that we could’ve taken action based on what we knew, rather than waiting around to prove everything and publish papers in Nature and Science talking about things we already knew.

We could have prepared for November and December of 2020 and then for November and December of 2021. But everyone kept saying, we don’t know if it’s going to come back. We knew it was going to come back and it makes me want to cry to think about it. We did nothing and hundreds of thousands of people died. We didn’t prepare nursing homes because we all got to the summer of 2020 and we said, cross our fingers.

We knew how tests worked. We knew about serial testing and why it was important for a public health approach. We knew that vaccines could have really good impacts once they were around. And if you were looking through the correct lens, we even knew that they weren’t going to stop transmission.

We didn’t have to live in a world where we were flying blind. We could have lived in a world where we’re knowledgeable. But instead, we chose almost across the board to will ourselves into this state of fear and anxiety.

And that really started in the earliest days. Almost the first experience I had was a lot like that movie with Jennifer Lawrence —Don’t Look Up.

none of this was complicated. You just had to ask a simple question: what would happen if you took away all immunity from an adult? Well, once you control for no immunity, adults are going to get very, very sick.

Of course, by and large, babies didn’t get very sick from this disease.Babies are immunologically naïve, but they are also resilient. A virus can tear up a baby, but a baby can repair its tissue so fast. Adults don’t have that. It’s just like a baby getting a cut. They’ll heal really quick

An adult getting a cut — you go by age, and every decade of age that you are, it’s going to take exponentially longer for that wound to heal. Eventually get to 80 or 90 and the wound can’t even heal. In the immunology world, this is called “tolerance.”

why are all these organ systems getting damaged when other viruses don’t seem to do that? It’s natural to think, it’s Covid — this is a weird disease. But it’s much more a story about immunity and how it develops than about the virus or the disease. None of our organ systems had any immune defenses around to help them out. And I think that the majority of post-acute sequelae and multi-organ complications and long Covid — they are not the result of the virus being a crazy different virus, but are a result of this virus replicating in an environment where there were such absent or exceedingly low defenses.

Is it the same whenever we encounter a virus for the first time?Think about travelers. Travelers get way more sick from a local disease than people who grew up with that virus. If you get malaria as a traveler, you’re much more likely to get really sick. You don’t see everyone in Nicaragua taking chloroquine every day. But you definitely see travelers taking it, because malaria can be deadly for adults.

What about, not severity, but post-acute complications — do we have long malaria? Do we have liver complications from dengue?

The really hard part of answering that question is there’s just not enough data on the frequency of long-term effects, because nothing like this has ever happened at such scale. It’s like everyone in Europe and North America suddenly traveled to a country where malaria was endemic.

Or think about H.I.V. It essentially kills your immune system, and once the immune barriers are down, other viruses that used to infect humans would get into tissues that we didn’t like them to get into. If there wasn’t such a clear signal of a loss of CD-4 T cells to explain it, people might still be scratching their heads and going, man, I wonder why all these patients are getting fungal infections. Well, there’s a virus there that’s depleting their immune system.

Covid is absolutely waking the world up to this — to the fact that there are really weird long-term sequelae to viruses when they infect organ systems that would normally be protected. And I think we’re going to find that more and more cancers are being attributed to viral infections.

It wasn’t that long ago that we first learned that most cases of cervical cancer were caused by H.P.V. — I think the 1980s. And now we have a vaccine for H.P.V. and rates of cervical cancer have fallen by two-thirds.

what about incidence? We’ve talked at a few points about how important it is to think about all of these questions in terms of the scale. What is the right scale for thinking about future long Covid, for instance, or other post-acute sequelae?

I think the absolute risk, per infection, is going down and down and down. That’s just true.

he U.K.’s Office of National Statistics, which shows a much lower risk of developing long Covid now, from reinfection, than from an initial infection earlier in the pandemic.

the worst is definitely behind us, which is a good thing, especially for people who worry that the problems will keep building and a lot of people — or even everyone — will get long Covid symptoms. I don’t think there’s a world where we’re looking at the babies of today dealing with long Covid at any meaningful scale.

a lot of the fear right now comes from the worst cases, and there’s a lot of worst cases. Even one of the people that I know well, I know in their mind they’re worried that they’ll never recover, but I think objectively they are recovering slowly. It might not be an eight month course. It might be a year and a half. But they will get better. Most of us will.

To contain such a pathogen, nations must develop a test and use it to identify infected people, isolate them, and trace those they’ve had contact with. That is what South Korea, Singapore, and Hong Kong did to tremendous effect. It is what the United States did not.

That a biomedical powerhouse like the U.S. should so thoroughly fail to create a very simple diagnostic test was, quite literally, unimaginable. “I’m not aware of any simulations that I or others have run where we [considered] a failure of testing,”

The testing fiasco was the original sin of America’s pandemic failure, the single flaw that undermined every other countermeasure. If the country could have accurately tracked the spread of the virus, hospitals could have executed their pandemic plans, girding themselves by allocating treatment rooms, ordering extra supplies, tagging in personnel, or assigning specific facilities to deal with COVID-19 cases.

None of that happened. Instead, a health-care system that already runs close to full capacity, and that was already challenged by a severe flu season, was suddenly faced with a virus that had been left to spread, untracked, through communities around the country.

With little room to surge during a crisis, America’s health-care system operates on the assumption that unaffected states can help beleaguered ones in an emergency.

That ethic works for localized disasters such as hurricanes or wildfires, but not for a pandemic that is now in all 50 states. Cooperation has given way to competition

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

Rudderless, blindsided, lethargic, and uncoordinated, America has mishandled the COVID-19 crisis to a substantially worse degree than what every health expert I’ve spoken with had feared. “Much worse,”

“Beyond any expectations we had,” said Lauren Sauer, who works on disaster preparedness at Johns Hopkins Medicine. “As an American, I’m horrified,” said Seth Berkley, who heads Gavi, the Vaccine Alliance. “The U.S. may end up with the worst outbreak in the industrialized world.”

it will be difficult—but not impossible—for the United States to catch up. To an extent, the near-term future is set because COVID-19 is a slow and long illness. People who were infected several days ago will only start showing symptoms now, even if they isolated themselves in the meantime. Some of those people will enter intensive-care units in early April

A “massive logistics and supply-chain operation [is] now needed across the country,” says Thomas Inglesby of Johns Hopkins Bloomberg School of Public Health. That can’t be managed by small and inexperienced teams scattered throughout the White House. The solution, he says, is to tag in the Defense Logistics Agency—a 26,000-person group that prepares the U.S. military for overseas operations and that has assisted in past public-health crises, including the 2014 Ebola outbreak.

The first and most important is to rapidly produce masks, gloves, and other personal protective equipment

it would also come at a terrible cost: SARS-CoV-2 is more transmissible and fatal than the flu, and it would likely leave behind many millions of corpses and a trail of devastated health systems.

This agency can also coordinate the second pressing need: a massive rollout of COVID-19 tests.

These measures will take time, during which the pandemic will either accelerate beyond the capacity of the health system or slow to containable levels. Its course—and the nation’s fate—now depends on the third need, which is social distancing.

There are now only two groups of Americans. Group A includes everyone involved in the medical response, whether that’s treating patients, running tests, or manufacturing supplies. Group B includes everyone else, and their job is to buy Group A more time. Group B must now “flatten the curve” by physically isolating themselves from other people to cut off chains of transmission.

Given the slow fuse of COVID-19, to forestall the future collapse of the health-care system, these seemingly drastic steps must be taken immediately, before they feel proportionate, and they must continue for several weeks.

Persuading a country to voluntarily stay at home is not easy, and without clear guidelines from the White House, mayors, governors, and business owners have been forced to take their own steps.

when the good of all hinges on the sacrifices of many, clear coordination matters—the fourth urgent need

Pundits and business leaders have used similar rhetoric, arguing that high-risk people, such as the elderly, could be protected while lower-risk people are allowed to go back to work. Such thinking is seductive, but flawed. It overestimates our ability to assess a person’s risk, and to somehow wall off the ‘high-risk’ people from the rest of society. It underestimates how badly the virus can hit ‘low-risk’ groups, and how thoroughly hospitals will be overwhelmed if even just younger demographics are falling sick.

A recent analysis from the University of Pennsylvania estimated that even if social-distancing measures can reduce infection rates by 95 percent, 960,000 Americans will still need intensive care.

There are only about 180,000 ventilators in the U.S. and, more pertinently, only enough respiratory therapists and critical-care staff to safely look after 100,000 ventilated patients. Abandoning social distancing would be foolish. Abandoning it now, when tests and protective equipment are still scarce, would be catastrophic.

If Trump stays the course, if Americans adhere to social distancing, if testing can be rolled out, and if enough masks can be produced, there is a chance that the country can still avert the worst predictions about COVID-19, and at least temporarily bring the pandemic under control. No one knows how long that will take, but it won’t be quick. “It could be anywhere from four to six weeks to up to three months,” Fauci said, “but I don’t have great confidence in that range.”

there are three possible endgames: one that’s very unlikely, one that’s very dangerous, and one that’s very long.

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

The second is that the virus does what past flu pandemics have done: It burns through the world and leaves behind enough immune survivors that it eventually struggles to find viable hosts. This “herd immunity” scenario would be quick, and thus tempting

The U.S. has fewer hospital beds per capita than Italy. A study released by a team at Imperial College London concluded that if the pandemic is left unchecked, those beds will all be full by late April. By the end of June, for every available critical-care bed, there will be roughly 15 COVID-19 patients in need of one.  By the end of the summer, the pandemic will have directly killed 2.2 million Americans,

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

there are no existing vaccines for coronaviruses—until now, these viruses seemed to cause diseases that were mild or rare—so researchers must start from scratch.

The first steps have been impressively quick. Last Monday, a possible vaccine created by Moderna and the National Institutes of Health went into early clinical testing. That marks a 63-day gap between scientists sequencing the virus’s genes for the first time and doctors injecting a vaccine candidate into a person’s arm. “It’s overwhelmingly the world record,” Fauci said.

The initial trial will simply tell researchers if the vaccine seems safe, and if it can actually mobilize the immune system. Researchers will then need to check that it actually prevents infection from SARS-CoV-2. They’ll need to do animal tests and large-scale trials to ensure that the vaccine doesn’t cause severe side effects. They’ll need to work out what dose is required, how many shots people need, if the vaccine works in elderly people, and if it requires other chemicals to boost its effectiveness.

No matter which strategy is faster, Berkley and others estimate that it will take 12 to 18 months to develop a proven vaccine, and then longer still to make it, ship it, and inject it into people’s arms.

as the status quo returns, so too will the virus. This doesn’t mean that society must be on continuous lockdown until 2022. But “we need to be prepared to do multiple periods of social distancing,” says Stephen Kissler of Harvard.

First: seasonality. Coronaviruses tend to be winter infections that wane or disappear in the summer. That may also be true for SARS-CoV-2, but seasonal variations might not sufficiently slow the virus when it has so many immunologically naive hosts to infect.

Second: duration of immunity. When people are infected by the milder human coronaviruses that cause cold-like symptoms, they remain immune for less than a year. By contrast, the few who were infected by the original SARS virus, which was far more severe, stayed immune for much longer.

scientists will need to develop accurate serological tests, which look for the antibodies that confer immunity. They’ll also need to confirm that such antibodies actually stop people from catching or spreading the virus. If so, immune citizens can return to work, care for the vulnerable, and anchor the economy during bouts of social distancing.

Aspects of America’s identity may need rethinking after COVID-19. Many of the country’s values have seemed to work against it during the pandemic. Its individualism, exceptionalism, and tendency to equate doing whatever you want with an act of resistance meant that when it came time to save lives and stay indoors, some people flocked to bars and clubs.

“We can keep schools and businesses open as much as possible, closing them quickly when suppression fails, then opening them back up again once the infected are identified and isolated. Instead of playing defense, we could play more offense.”

The vaccine may need to be updated as the virus changes, and people may need to get revaccinated on a regular basis, as they currently do for the flu. Models suggest that the virus might simmer around the world, triggering epidemics every few years or so. “But my hope and expectation is that the severity would decline, and there would be less societal upheaval,”

After infections begin ebbing, a secondary pandemic of mental-health problems will follow.

But “there is also the potential for a much better world after we get through this trauma,”

Testing kits can be widely distributed to catch the virus’s return as quickly as possible. There’s no reason that the U.S. should let SARS-CoV-2 catch it unawares again, and thus no reason that social-distancing measures need to be deployed as broadly and heavy-handedly as they now must be.

Pandemics can also catalyze social change. People, businesses, and institutions have been remarkably quick to adopt or call for practices that they might once have dragged their heels on, including working from home, conference-calling to accommodate people with disabilities, proper sick leave, and flexible child-care arrangements.

Perhaps the nation will learn that preparedness isn’t just about masks, vaccines, and tests, but also about fair labor policies and a stable and equal health-care system. Perhaps it will appreciate that health-care workers and public-health specialists compose America’s social immune system, and that this system has been suppressed.

Attitudes to health may also change for the better. The rise of HIV and AIDS “completely changed sexual behavior among young people who were coming into sexual maturity at the height of the epidemic,”

Years of isolationist rhetoric had consequences too.

“People believed the rhetoric that containment would work,” says Wendy Parmet, who studies law and public health at Northeastern University. “We keep them out, and we’ll be okay. When you have a body politic that buys into these ideas of isolationism and ethnonationalism, you’re especially vulnerable when a pandemic hits.”

Pandemics are democratizing experiences. People whose privilege and power would normally shield them from a crisis are facing quarantines, testing positive, and losing loved ones. Senators are falling sick. The consequences of defunding public-health agencies, losing expertise, and stretching hospitals are no longer manifesting as angry opinion pieces, but as faltering lungs.

After COVID-19, attention may shift to public health. Expect to see a spike in funding for virology and vaccinology, a surge in students applying to public-health programs, and more domestic production of medical supplies.

The lessons that America draws from this experience are hard to predict, especially at a time when online algorithms and partisan broadcasters only serve news that aligns with their audience’s preconceptions.

“The transitions after World War II or 9/11 were not about a bunch of new ideas,” he says. “The ideas are out there, but the debates will be more acute over the next few months because of the fluidity of the moment and willingness of the American public to accept big, massive changes.”

One could easily conceive of a world in which most of the nation believes that America defeated COVID-19. Despite his many lapses, Trump’s approval rating has surged. Imagine that he succeeds in diverting blame for the crisis to China, casting it as the villain and America as the resilient hero.

One could also envisage a future in which America learns a different lesson. A communal spirit, ironically born through social distancing, causes people to turn outward, to neighbors both foreign and domestic. The election of November 2020 becomes a repudiation of “America first” politics. The nation pivots, as it did after World War II, from isolationism to international cooperation

The U.S. leads a new global partnership focused on solving challenges like pandemics and climate change.

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

On the Global Health Security Index, a report card that grades every country on its pandemic preparedness, the United States has a score of 83.5—the world’s highest. Rich, strong, developed, America is supposed to be the readiest of nations. That illusion has been shattered. Despite months of advance warning as the virus spread in other countries, when America was finally tested by COVID-19, it failed.

“There cannot be any daylight between what the research shows — really impressive but incomplete protection — and how it is described,” said Dr. Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center in New York.

This opens the door to the skeptics who think the government is sugarcoating the science,” Dr. Bach said, “and completely undermines any remaining argument why people should keep wearing masks after being vaccinated.”

Clinical trials of the vaccines were designed only to assess whether the vaccines prevent serious illness and death. The research from the C.D.C. on Monday brought the welcome conclusion that the vaccines are also extremely effective at preventing infection.

The study enrolled 3,950 health care workers, emergency responders and others at high risk of infection. The participants swabbed their noses each week and sent the samples in for testing, which allowed federal researchers to track all infections, symptomatic or not. Two weeks after vaccination, the vast majority of vaccinated people remained virus-free, the study found.

Follow-up data from clinical trials support that finding. In results released by Pfizer and BioNTech on Wednesday, for example, 77 people who received the vaccine had a coronavirus infection, compared with 850 people who got a placebo.

“Clearly, some vaccinated people do get infected,” Dr. Duprex said. “We’re stopping symptoms, we’re keeping people out of hospitals. But we’re not making them completely resistant to an infection.”

The number of vaccinated people who become infected is likely to be higher among those receiving vaccines made by Johnson & Johnson and AstraZeneca, which have a lower efficacy, experts said. (Still, those vaccines are worth taking, because they uniformly prevent serious illness and death.)

Given the rising numbers, it’s especially important that immunized people continue to protect those who have not yet been immunized against the virus, experts said.

“Vaccinated people should not be throwing away their masks at this point,” Dr. Moore said. “This pandemic is not over.”

And suppose it takes five days between a person’s getting infected and their infecting others. After 30 days, the more transmissible virus is now causing 26, or 64, times as many new cases as the less transmissible one.

Not every case will be mild, though, and even a small hospitalization rate on top of a huge case number will be a big number.

Now, as my colleague Ed Yong reports, Omicron could push a collapsing health-care system further into disaster. Hospitals are already dealing with the flu and other winter viruses. They’re already canceling elective surgeries.

If there are no changes to behavior or policy, this year’s winter wave would peak at about double the hospitalizations of last winter at its worst, and 20 percent more deaths, according to the most pessimistic of projections

The most optimistic projection sees a caseload similar to last winter’s, but hospitalizations and deaths at about half of where they were back then, assuming the vaccines keep up their very high protection against severe illness.

If that holds, it’s a “huge decrease,” Meyers says, and one that matches the assumptions of her team’s grimmer—but not grimmest—projections. When they modeled scenarios where vaccine effectiveness against hospitalization dropped by about that much, they saw a difference of tens of thousands of deaths.

Very preliminary data from South Africa’s largest health insurer suggest that two doses of the Pfizer-BioNTech vaccine were 70 percent effective at preventing hospitalization from Omicron infections, down from 93 percent before.

Vaccine protection against severe illness should be more durable than it is against infection, but may still take a hit

The available evidence on Omicron’s inherent severity is likely to be biased in ways that make it appear more promising. First of all, hospitalizations lag infections.

Second, the first people infected may skew young and are thus more likely to have mild cases regardless of the variant

third, some of the mildness attributed to the virus may result instead from existing immunity. In South Africa, where doctors are reporting relatively low hospitalizations compared with previous waves, many cases are probably reinfections

The South Africa health-insurer data suggest that Omicron might carry a 29 percent lower risk of hospitalization than the original virus, when adjusted for risk factors including age, sex, vaccination status, and documented prior infection—but many prior infections may be undocumented, which would make the reduction in risk seem bigger than it really is. (A recent analysis of early U.K. cases found “at most, limited changes in severity compared with Delta.”)

Either way, in the short run, we will have a massive number of Omicron cases on top of a massive number of Delta cases. Together they will infect huge numbers of people, vaccinated or not

Researchers believe the incubation period before symptoms is roughly five days on average. In studying the pattern of illness, epidemiologists have made the dismaying discovery that people start shedding the virus — potentially making others sick — in advance of symptoms.

The bulldozer nature of coronavirus means widespread severe illnesses and deaths from covid-19 can happen with terrifying speed.

a large percentage of the world’s population, potentially billions of people, could become infected within the next couple of years. Frantic efforts to develop a safe and effective vaccine are likely to take a year or more.

covid-19 may be many times as lethal for an infected person as seasonal flu.

the virus has a gift for stealth transmission. It seeds itself in communities far and wide,

But on Jan. 23, China imposed extreme travel restrictions and soon put hundreds of millions of people into some form of lockdown as authorities aggressively limited social contact. The R0 plummeted below 1, and the epidemic has been throttled in China, at least for now.

R0, pronounced “R naught.” That is the average number of new infections generated by each infected person.

he R0 is not an intrinsic feature of the virus. It can be lowered through containment, mitigation and ultimately “herd immunity,”

In the early days in China, before the government imposed extreme travel restrictions in Wuhan and nearby areas, and before everyone realized exactly how bad the epidemic might be, the R0 was 2.38, according to a study published in the journal Science. That is a highly contagious disease.

The pandemic appears to be largely driven by direct, human-to-human transmission. That is why public health officials have told people to engage in social distancing

its ability to spread depends also on the vulnerability of the human population, including the density of the community.

Without a vaccine or a drug to stop infections, the best hope is to break the chain of transmission one infection at a time

“Social distancing is building speed bumps so that we can slow the spread of the virus. We have to respect the speed bumps,”

the efficacy of social distancing “is the million-dollar question right now.”

She compared the current public measures to what happened during the 1918 influenza pandemic that killed an estimated 675,000 people in the United States, and in which some cities were more careful than others about enforcing social distancing.

“The USA is currently in a natural experiment of sorts, which each state implementing their own version of social distancing,” she said. “We will be able to compare the efficacy of these various public health policies, but not until more time has passed.”

Not only must people limit their direct contact, they need to limit the amount that their paths overlap, because the virus can linger on surfaces.

The virus degrades outside a host because of exposure to moisture and sunlight, or from drying out

in pristine laboratory conditions, some SARS-CoV-2 particles can remain potentially viable on metal or plastic for up to three days.

Absent hard data, limiting contact with shared surfaces, such as door handles or checkout machines, and frequent hand-washing is highly advisable.

people have some innate, mechanical defenses against viruses just like they do against pollen and dust, Taubenberger noted. Cells in the respiratory tract have tiny hairlike projections, called cilia, that move mucus toward the throat in a manner that helps clear invasive particles. This is not our body’s first viral rodeo.

Based on this seroprevalence data, the authors estimate that in Santa Clara County the true infection fatality rate is somewhere in the range of 0.12% to 0.2%—far closer to seasonal influenza than to the original, case-based estimates.

In New York City, a study published in the New England Journal of Medicine examined 215 women entering two hospitals to give birth between March 22 and April 4. These patients had a Covid-19 infection rate over 15%. Of expectant mothers who tested positive for active infections, 88% were asymptomatic at the time of admission. That infection rate is about 10 times the rate of known cases in the city

Similar proportions of infections to cases are now being discovered around the world: 30 times in Robbio, Italy; 10 times in Iceland; 14 times in Gangelt, Germany; 27 times in Denmark. Germany and Denmark are now leading Europe in reopening their economies in the coming week

a path forward demands continued monitoring of seroprevalence as well as new case testing, identifying and protecting those most vulnerable to more serious or even fatal infections, and supporting hospital capacity to handle surges of respiratory intensive-care patients.

The science to support better modeling and decision making is rapidly becoming available. One hopes that it will inform better policy decisions.

the coronavirus more often infects clusters of family members, friends and work colleagues,

“You can contain clusters,” Dr. Heymann said. “You need to identify and stop discrete outbreaks, and then do rigorous contact tracing.”

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.

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.

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.

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

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.

medical experts should be at the microphone now to explain complex ideas like epidemic curves, social distancing and off-label use of drugs.

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.

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.

“At this point in the emergency, there’s little merit in spending time on what we should have done or who’s at fault,”

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.

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.

Stop transmission within cities

the weaker the freeze, the more people die in overburdened hospitals — and the longer it ultimately takes for the economy to restart.

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.

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.

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.

Fix the testing mess

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.

Isolate the infected

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.

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.

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

Make masks ubiquitous

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.

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.

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

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

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.

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

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.

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.

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.

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

Preserve vital services

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

“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

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.

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.

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

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

Decide when to close schools

Recruit volunteers

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.

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.

“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

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.

An alternative is to harvest protective antibodies from the blood of people who have survived the illness,

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

testing those candidate vaccines for safety and effectiveness takes time.

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.

Reach out to other nations

Ventilation systems in schools, nursing homes, residences and businesses may need to minimize recirculating air and add powerful new filters.

in an open letter to the W.H.O., 239 scientists in 32 countries have outlined the evidence showing that smaller particles can infect people, and are calling for the agency to revise its recommendations

Whether carried aloft by large droplets that zoom through the air after a sneeze, or by much smaller exhaled droplets that may glide the length of a room, these experts said, the coronavirus is borne through air and can infect people when inhaled

But the infection prevention and control committee in particular, experts said, is bound by a rigid and overly medicalized view of scientific evidence, is slow and risk-averse in updating its guidance and allows a few conservative voices to shout down dissent.

“If we started revisiting airflow, we would have to be prepared to change a lot of what we do,” she said. “I think it’s a good idea, a very good idea, but it will cause an enormous shudder through the infection control society.”

In early April, a group of 36 experts on air quality and aerosols urged the W.H.O. to consider the growing evidence on airborne transmission of the coronavirus. The agency responded promptly, calling Lidia Morawska, the group’s leader and a longtime W.H.O. consultant, to arrange a meeting.

But the discussion was dominated by a few experts who are staunch supporters of handwashing and felt it must be emphasized over aerosols, according to some participants, and the committee’s advice remained unchanged.

Dr. Morawska and others pointed to several incidents that indicate airborne transmission of the virus, particularly in poorly ventilated and crowded indoor spaces. They said the W.H.O. was making an artificial distinction between tiny aerosols and larger droplets, even though infected people produce both.

We’ve known since 1946 that coughing and talking generate aerosols,

Scientists have not been able to grow the coronavirus from aerosols in the lab.

Most of the samples in those experiments have come from hospital rooms with good air flow that would dilute viral levels.

In most buildings, she said, “the air-exchange rate is usually much lower, allowing virus to accumulate in the air and pose a greater risk.”

The W.H.O. also is relying on a dated definition of airborne transmission, Dr. Marr said. The agency believes an airborne pathogen, like the measles virus, has to be highly infectious and to travel long distances.

Dr. Marr and others said the coronavirus seemed to be most infectious when people were in prolonged contact at close range, especially indoors, and even more so in superspreader events — exactly what scientists would expect from aerosol transmission.

Experts all agree that the coronavirus does not behave that way.

“We have this notion that airborne transmission means droplets hanging in the air capable of infecting you many hours later, drifting down streets, through letter boxes and finding their way into homes everywhere,”

The agency lagged behind most of its member nations in endorsing face coverings for the public. While other organizations, including the C.D.C., have long since acknowledged the importance of transmission by people without symptoms, the W.H.O. still maintains that asymptomatic transmission is rare.

Many experts said the W.H.O. should embrace what some called a “precautionary principle” and others called “needs and values” — the idea that even without definitive evidence, the agency should assume the worst of the virus, apply common sense and recommend the best protection possible.

“There is no incontrovertible proof that SARS-CoV-2 travels or is transmitted significantly by aerosols, but there is absolutely no evidence that it’s not,

So at the moment we have to make a decision in the face of uncertainty, and my goodness, it’s going to be a disastrous decision if we get it wrong,” she said. “So why not just mask up for a few weeks, just in case?”

he agency also must consider the needs of all its member nations, including those with limited resources, and make sure its recommendations are tempered by “availability, feasibility, compliance, resource implications,” she said.

if the W.H.O. were to push for rigorous control measures in the absence of proof, hospitals in low- and middle-income countries may be forced to divert scarce resources from other crucial programs.

That’s the balance that an organization like the W.H.O. has to achieve,” he said. “It’s the easiest thing in the world to say, ‘We’ve got to follow the precautionary principle,’ and ignore the opportunity costs of that.”

In interviews, other scientists criticized this view as paternalistic. “‘We’re not going to say what we really think, because we think you can’t deal with it?’ I don’t think that’s right,”

Even cloth masks, if worn by everyone, can significantly reduce transmission, and the W.H.O. should say so clearly, he added.

The W.H.O. tends to describe “an absence of evidence as evidence of absence,” Dr. Aldis added. In April, for example, the W.H.O. said, “There is currently no evidence that people who have recovered from Covid-19 and have antibodies are protected from a second infection.”

The statement was intended to indicate uncertainty, but the phrasing stoked unease among the public and earned rebukes from several experts and journalists. The W.H.O. later walked back its comments.

In a less public instance, the W.H.O. said there was “no evidence to suggest” that people with H.I.V. were at increased risk from the coronavirus. After Joseph Amon, the director of global health at Drexel University in Philadelphia who has sat on many agency committees, pointed out that the phrasing was misleading, the W.H.O. changed it to say the level of risk was “unknown.”

But W.H.O. staff and some members said the critics did not give its committees enough credit.“Those that may have been frustrated may not be cognizant of how W.H.O. expert committees work, and they work slowly and deliberately,”

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.