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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.

Dr. Gallo is leading the charge to test the O.P.V. live polio vaccine as a treatment for coronavirus.

B.C.G. may actually be able to ramp up the body’s initial immune response in ways that reduce the amount of virus in the body, such that an inflammatory response never occurs.

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.

scientists and administrators in the E.P.A.’s Office of Water were alarmed in late May when a top Trump administration appointee insisted upon the rewriting of a rule to make it harder to track the health consequences of the chemical, and therefore regulate it.

The chemical, perfluorooctanoic acid, or PFOA, has been linked to kidney cancer, birth defects, immune system disorders and other serious health problems.

The revision was among more than a dozen demanded by the appointee, Nancy B. Beck, after she joined the E.P.A.’s toxic chemical unit in May as a top deputy. For the previous five years, she had been an executive at the American Chemistry Council, the chemical industry’s main trade association.

The E.P.A.’s abrupt new direction on legacy chemicals is part of a broad initiative by the Trump administration to change the way the federal government evaluates health and environmental risks associated with hazardous chemicals, making it more aligned with the industry’s wishes.

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.

But for those hoping that 25 percent represents a true ceiling for pandemic spread in a given community, well, it almost certainly does not, considering that recent serological surveys have shown that perhaps 93 percent of the population of Iquitos, Peru, has contracted the disease; as have more than half of those living in Indian slums; and as many as 68 percent in particular neighborhoods of New York City

overshoot of that scale would seem unlikely if the “true” threshold were as low as 20 or 25 percent.

But, of course, that threshold may not be the same in all places, across all populations, and is surely affected, to some degree, by the social behavior taken to protect against the spread of the disease.

we probably err when we conceive of group immunity in simplistically binary terms. While herd immunity is a technical term referring to a particular threshold at which point the disease can no longer spread, some amount of community protection against that spread begins almost as soon as the first people are exposed, with each case reducing the number of unexposed and vulnerable potential cases in the community by one

you would not expect a disease to spread in a purely exponential way until the point of herd immunity, at which time the spread would suddenly stop. Instead, you would expect that growth to slow as more people in the community were exposed to the disease, with most of them emerging relatively quickly with some immune response. Add to that the effects of even modest, commonplace protections — intuitive social distancing, some amount of mask-wearing — and you could expect to get an infection curve that tapers off well shy of 60 percent exposure.

Looking at the data, we see that transmissions in many severely impacted states began to slow down in July, despite limited interventions. This is especially notable in states like Arizona, Florida, and Texas. While we believe that changes in human behavior and changes in policy (such as mask mandates and closing of bars/nightclubs) certainly contributed to the decrease in transmission, it seems unlikely that these were the primary drivers behind the decrease. We believe that many regions obtained a certain degree of temporary herd immunity after reaching 10-35 percent prevalence under the current conditions. We call this 10-35 percent threshold the effective herd immunity threshold.

Indeed, that is more or less what was recently found by Youyang Gu, to date the best modeler of pandemic spread in the U.S

he cautioned again that he did not mean to imply that the natural herd-immunity level was as low as 10 percent, or even 35 percent. Instead, he suggested it was a plateau determined in part by better collective understanding of the disease and what precautions to take

Gu estimates national prevalence as just below 20 percent (i.e., right in the middle of his range of effective herd immunity), it still counts, I think, as encouraging — even if people in hard-hit communities won’t truly breathe a sigh of relief until vaccines arrive.

If you can get real protection starting at 35 percent, it means that even a mediocre vaccine, administered much more haphazardly to a population with some meaningful share of vaccination skeptics, could still achieve community protection pretty quickly. And that is really significant — making both the total lack of national coordination on rollout and the likely “vaccine wars” much less consequential.

At least 20 percent of the public, and perhaps 50 percent, had some preexisting, cross-protective T-cell response to SARS-CoV-2, according to one much-discussed recent paper. An earlier paper had put the figure at between 40 and 60 percent. And a third had found an even higher prevalence: 81 percent.

The T-cell story is similarly encouraging in its big-picture implications without being necessarily paradigm-changing

These numbers suggest their own heterogeneity — that different populations, with different demographics, would likely exhibit different levels of cross-reactive T-cell immune response

The most optimistic interpretation of the data was given to me by Francois Balloux, a somewhat contrarian disease geneticist and the director of the University College of London’s Genetics Institute

According to him, a cross-reactive T-cell response wouldn’t prevent infection, but would probably mean a faster immune response, a shorter period of infection, and a “massively” reduced risk of severe illness — meaning, he guessed, that somewhere between a third and three-quarters of the population carried into the epidemic significant protection against its scariest outcomes

the distribution of this T-cell response could explain at least some, and perhaps quite a lot, of COVID-19’s age skew when it comes to disease severity and mortality, since the young are the most exposed to other coronaviruses, and the protection tapers as you get older and spend less time in environments, like schools, where these viruses spread so promiscuously.

Balloux told me he believed it was also possible that the heterogeneous distribution of T-cell protection also explains some amount of the apparent decline in disease severity over time within countries on different pandemic timelines — a phenomenon that is more conventionally attributed to infection spreading more among the young, better treatment, and more effective protection of the most vulnerable (especially the old).

Going back to Youyang Gu’s analysis, what he calls the “implied infection fatality rate” — essentially an estimated ratio based on his modeling of untested cases — has fallen for the country as a whole from about one percent in March to about 0.8 percent in mid-April, 0.6 percent in May, and down to about 0.25 percent today.

even as we have seemed to reach a second peak of coronavirus deaths, the rate of death from COVID-19 infection has continued to decline — total deaths have gone up, but much less than the number of cases

In other words, at the population level, the lethality of the disease in America has fallen by about three-quarters since its peak. This is, despite everything that is genuinely horrible about the pandemic and the American response to it, rather fantastic.

there may be some possible “mortality displacement,” whereby the most severe cases show up first, in the most susceptible people, leaving behind a relatively protected population whose experience overall would be more mild, and that T-cell response may play a significant role in determining that susceptibility.

That, again, is Balloux’s interpretation — the most expansive assessment of the T-cell data offered to me

The most conservative assessment came from Sarah Fortune, the chair of Harvard’s Department of Immunology

Fortune cautioned not to assume that cross-protection was playing a significant role in determining severity of illness in a given patient. Those with such a T-cell response, she told me, would likely see a faster onset of robust response, yes, but that may or may not yield a shorter period of infection and viral shedding

Most of the scientists, doctors, epidemiologists, and immunologists I spoke to fell between those two poles, suggesting the T-cell cross-immunity findings were significant without necessarily being determinative — that they may help explain some of the shape of pandemic spread through particular populations, but only some of the dynamics of that spread.

he told me he believed, in the absence of that data, that T-cell cross-immunity from exposure to previous coronaviruses “might explain different disease severity in different people,” and “could certainly be part of the explanation for the age skew, especially for why the very young fare so well.”

the headline finding was quite clear and explicitly stated: that preexisting T-cell response came primarily via the variety of T-cells called CD4 T-cells, and that this dynamic was consistent with the hypothesis that the mechanism was inherited from previous exposure to a few different “common cold” coronaviruses

“This potential preexisting cross-reactive T-cell immunity to SARS-CoV-2 has broad implications,” the authors wrote, “as it could explain aspects of differential COVID-19 clinical outcomes, influence epidemiological models of herd immunity, or affect the performance of COVID-19 candidate vaccines.”

“This is at present highly speculative,” they cautioned.

“That amount of memory would likely prevent the vast majority of people from getting hospitalized disease, severe disease, for many years,” said Shane Crotty, a virologist at the La Jolla Institute of Immunology who co-led the new study.

A study published last week also found that people who have recovered from Covid-19 have powerful and protective killer immune cells even when antibodies are not detectable.

These studies “are all by and large painting the same picture, which is that once you get past those first few critical weeks, the rest of the response looks pretty conventional,” said Deepta Bhattacharya, an immunologist at the University of Arizona

A small number of infected people in the new study did not have long-lasting immunity after recovery, perhaps because of differences in the amounts of coronavirus they were exposed to.

Although antibodies in the blood are needed to block the virus and forestall a second infection — a condition known as sterilizing immunity — immune cells that “remember” the virus more often are responsible for preventing serious illness.

More often, people become infected a second time with a particular pathogen, and the immune system recognizes the invader and quickly extinguishes the infection. The coronavirus in particular is slow to do harm, giving the immune system plenty of time to kick into gear.

“It may be terminated fast enough that not only are you not experiencing any symptoms but you are not infectious,” Dr. Sette said.

Dr. Sette and his colleagues recruited 185 men and women, aged 19 to 81, who had recovered from Covid-19. The majority had mild symptoms not requiring hospitalization

The team tracked four components of the immune system: antibodies, B cells that make more antibodies as needed; and two types of T cells that kill other infected cells.

He and his colleagues found that antibodies were durable, with modest declines at six to eight months after infection, although there was a 200-fold difference in the levels among the participants.

The study is the first to chart the immune response to a virus in such granular detail, experts said. “For sure, we have no priors here,” Dr. Gommerman said. “We’re learning, I think for the first time, about some of the dynamics of these populations through time.”

Exactly how long immunity lasts is hard to predict, because scientists don’t yet know what levels of various immune cells are needed to protect from the virus. But studies so far have suggested that even small numbers of antibodies or T and B cells may be enough to shield those who have recovered.

“Whether the Delta variant is already at that plateau, or whether there’s going to be further increases before it gets to that plateau, I can’t say. But I do think that plateau exists.”

Antibodies, which can prevent the virus from entering our cells, are engineered to latch onto specific molecules on the surface of the virus, snapping into place like puzzle pieces. But genetic mutations in the virus can change the shape of those binding sites.

“If you change that shape, you can make it impossible for an antibody to do its job,”

But as more people acquire antibodies against the virus, mutations that allow the virus to slip past these antibodies will become even more advantageous.

The good news is that there are many different kinds of antibodies, and a variant with a few new mutations is unlikely to escape them all, experts said.

its sleeve to counteract the evolution of the virus,” Dr. Pepper said. “Knowing that there is this complex level of diversity in the immune system allows me to sleep better at night.”

“It’s a lot harder to evade T cell responses than antibody responses,”

And then there are B cells, which generate our army of antibodies. Even after we clear the infection, the body keeps churning out B cells for a while, deliberately introducing small genetic mutations. The result is an enormously diverse collection of B cells producing an array of antibodies, some of which might be a good match for the next variant that comes along.

Whether the virus will become more virulent — that is, whether it will cause more serious disease — is the hardest to predict,

Unlike transmissibility or immune evasion, virulence has no inherent evolutionary advantage.

Some scientists predict that the virus will ultimately be much like the flu, which can still cause serious illness and death, especially during seasonal surges.

“The virus has no interest in killing us,” Dr. Metcalf said. “Virulence only matters for the virus if it works for transmission.”

It is too early to say whether SARS-CoV-2 will change in virulence over the long-term. There could certainly be trade-offs between virulence and transmission; variants that make people too sick too quickly may not spread very far.

Then again, this virus spreads before people become severely ill. As long as that remains true, the virus could become more virulent without sacrificing transmissibility.

Moreover, the same thing that makes the virus more infectious — faster replication or tighter binding to our cells — could also make it more virulent.

Although many possible paths remain open to us, what is certain is that SARS-CoV-2 will not stop evolving — and that the arms race between the virus and us is just beginning.

We lost the first few rounds, by allowing the virus to spread unchecked, but we still have powerful weapons to bring to the fight. The most notable are highly effective vaccines, developed at record speed. “I think there is hope in the fact that the SARS-CoV-2 vaccines at this point are more effective than flu vaccines have probably ever been,”

“I have great faith that we can sort any detrimental evolutionary trajectories out by improving our current or next generation vaccines,”

be you have a re-infection, but it’s relatively mild, which also boosts your immunity,”

rising vaccination rates may already be suppressing new mutations.And the evolution rate could also slow down as the virus becomes better adapted to humans.

“There’s low-hanging fruit,” Dr. Lauring said. “So there are certain ways it can evolve and make big improvements, but after a while there aren’t areas to improve — it’s figured out all the easy ways to improve.”

Eventually, as viral evolution slows down and our immune systems catch up, we will reach an uneasy equilibrium with the virus, scientists predict. We will never extinguish it, but it will smolder rather than rage.

So far, studies suggest that our antibody, T cell and B cell responses are all working as expected when it comes to SARS-CoV-2. “This virus is mostly playing by immunological rules we understand,”

Others are more optimistic. “My guess is that one day this is going to be another cause of the common cold,”

There are four other coronaviruses that have become endemic in human populations. We are exposed to them early and often, and all four mostly cause run-of-the-mill colds.

much of the world remains unvaccinated, and this virus has already proved capable of surprising us. “We should be somewhat cautious and humble about trying to predict what it is capable of doing in the future,”

While we can’t guard against every eventuality, we can tip the odds in our favor by expanding viral surveillance, speeding up global vaccine distribution and tamping down transmission until more people can be vaccinated

The future, he said, “depends much, much more on what humans do than on what the virus does.”

One of the first questions experts asked me was whether my family was vaccinated. Yes, I said: My husband and I are vaccinated and boosted, and our kids are vaccinated but not yet boosted. This is a relevant question because, if you’re exposed to the virus that causes Covid-19, “your immune system kicks into action a lot faster if you’re vaccinated versus not vaccinated,”

First, the swift immune reaction slows the rate of viral reproduction and spread. “This is what the vaccines are there for — to educate your immune system so that it gets a jump on the invaders before they are able to replicate out of control,”

Because the virus doesn’t replicate as quickly in vaccinated people, they may be less likely to test positive for Covid-19 after coronavirus exposure, because their immune system “keeps the viral load below the level of detection,”

It’s possible, then, that my husband and son did catch Covid-19, but their vaccinated immune systems fended off the infection so well that they never had enough viral proteins in their nose or throat to test positive. And their continual negative tests probably meant that they were never that contagious

If my husband and son never tested positive, why did they feel sick? Even if a vaccinated person doesn’t have much virus in their body, they can still have powerful Covid symptoms

That’s because many illness symptoms — fever, malaise, runny nose, fatigue — are actually caused by the immune system’s response to the virus, rather than the virus itself

And as for why I felt fine, Dr. Morrison said that perhaps my immune system fought off the incoming virus so quickly that I didn’t even have a chance to feel sick. “It sounds to me like you were definitely exposed,”

maybe I had high levels of vaccine antibodies or immune cells called T cells that were able to kill the invading virus before it had a chance to alert the parts of my immune system that would incite symptoms.

All this said, nobody really knows what happened to me, my son or my husband. When it comes to understanding how Covid-19 affects the body, “there are so many open questions,”

people can have different experiences for many different reasons. For instance, Dr. Andino said, it’s possible that the virus was replicating in parts of my husband’s or my son’s body that the tests didn’t reach

Research suggests that the coronavirus can replicate in the pancreas, heart, brain, kidneys and other organs, although vaccination may reduce the chance that the virus spreads outside the respiratory system.

Dr. Andino said that he and his colleagues have been conducting studies in which they follow and repeatedly test entire households after one person in the home tests positive for Covid-19. “What we see is exactly what you described — that some people in the household don’t test positive,”