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“This virus has a surface protein that is primed to lock on that receptor and slip its RNA into the cell,”

Once inside, that RNA inserts itself into the cell’s own replication machinery and makes multiple copies of the virus. These burst out of the cell, and the infection spreads. Antibodies generated by the body’s immune system eventually target the virus and in most cases halt its progress.

“A Covid-19 infection is generally mild, and that really is the secret of the virus’s success,” adds Ball. “Many people don’t even notice they have got an infection and so go around their work, homes and supermarkets infecting others.”

the virus can cause severe problems. This happens when it moves down the respiratory tract and infects the lungs, which are even richer in cells with Ace-2 receptors. Many of these cells are destroyed, and lungs become congested with bits of broken cell. In these cases, patients will require treatment in intensive care.

Even worse, in some cases, a person’s immune system goes into overdrive, attracting cells to the lungs in order to attack the virus, resulting in inflammation

This process can run out of control, more immune cells pour in, and the inflammation gets worse. This is known as a cytokine storm.

Just why cytokine storms occur in some patients but not in the vast majority is unclear

Doctors examining patients recovering from a Covid-19 infection are finding fairly high levels of neutralising antibodies in their blood. These antibodies are made by the immune system, and they coat an invading virus at specific points, blocking its ability to break into cells.

Instead, most virologists believe that immunity against Covid-19 will last only a year or two. “That is in line with other coronaviruses that infect humans,

“It is clear that immune responses are being mounted against Covid-19 in infected people,” says virologist Mike Skinner of Imperial College London. “And the antibodies created by that response will provide protection against future infections – but we should note that it is unlikely this protection will be for life.”

“That means that even if most people do eventually become exposed to the virus, it is still likely to become endemic – which means we would see seasonal peaks of infection of this disease. We will have reached a steady state with regard to Covid-19.”

Skinner is doubtful. “We have got to consider this pandemic from the virus’s position,” he says. “It is spreading round the world very nicely. It is doing OK. Change brings it no benefit.”

In the end, it will be the development and roll-out of an effective vaccine that will free us from the threat of Covid-19,

the journal Nature reported that 78 vaccine projects had been launched round the globe – with a further 37 in development.

vaccines require large-scale safety and efficacy studies. Thousands of people would receive either the vaccine itself or a placebo to determine if the former were effective at preventing infection from the virus which they would have encountered naturally. That, inevitably, is a lengthy process.

some scientists have proposed a way to speed up the process – by deliberately exposing volunteers to the virus to determine a vaccine’s efficacy.

Volunteers would have to be young and healthy, he stresses: “Their health would also be closely monitored, and they would have access to intensive care and any available medicines.”

The result could be a vaccine that would save millions of lives by being ready for use in a much shorter time than one that went through standard phase three trials.

phase-three trials are still some way off, so we have time to consider the idea carefully.”

She and others emphasized the apparent lack of severe health repercussions from reinfection — and the lack of evidence that reinfection is common.

Nearly 4 percent of people who had a previous infection were reinfected, an almost identical rate to those with no history of infection.

“Basically, it’s saying vaccination actually needs to be better than natural immunity. But vaccination is better than natural immunity.”

The study backs up recent laboratory data from South African researchers analyzing blood plasma from recovered patients. Nearly half of the plasma samples had no detectable ability to block the variant from infecting cells in a laboratory dish

The good news is that vaccine trials from Johnson & Johnson and Novavax show that vaccines can work — even against the B.1.351 variant, and particularly in preventing severe illness.

Novavax did not provide a breakdown of mild, moderate and severe cases, but severe cases of covid-19 were rare in the trial, suggesting that reinfection is unlikely to send people to the hospital.

“It is not surprising to see reinfection in individuals who are convalescent. And it would not be surprising to see infection in people who are vaccinated, especially a few months out from vaccine,”

“The key is not whether people get reinfected, it’s whether they get sick enough to be hospitalized.

“If the data holds true, it means we will need to walk the public back on the idea of how close we are to the finish line for ending this pandemic.”

Projections created by data scientist Youyang Gu — whose pandemic models have been cited by the Centers for Disease Control and Prevention — suggest that about 65 percent of America’s population will reach immunity by June 1. But built into that 65 percent is roughly 20 percent having immunity from past infections only.

In a separate study, scientists at Rockefeller University in New York took blood plasma from people who had been vaccinated and found that vaccine-generated antibodies were largely able to block mutations found on the B.1.351 variant.

I think the fact that we … now have data from two vaccines indicating that we can prevent serious disease, even against the new variant, is hopeful,”

A future concern needing close monitoring is whether the reformulation of vaccines to keep up with the evolving virus could drive the virus to continue evolving.

There is also a concern that subpar immunity could allow new resistant variants to emerge. That possibility, Nussenzweig said, is one reason that people should get both doses of a vaccine, on time.

The WHO, CDC and other bureaucracies initially failed to quickly realize that the benefits of masks compound, simply because two people are wearing them and you have to look at the interaction.

Let us say (to simplify) that masks reduce both transmission and reception to p. What effect on the R0(that is, the rate of spreading of the infection)?

Simply the naive approach (used by the CDC/WHO bureaucrats and other imbeciles) is to say if masks reduce the transmission probability to ¼, one would think it would then drop from, say R0= 5, to R0=1 ¼. Yuuge, but there is better.

For one should count both sides. Under our simplification, with p=1/4 we get R0'= p² R0 . The drop in R becomes 93.75%! You divide R by 16! Even with masks working at 50% we get a 75% drop in R0.

Second error: Missing the Nonlinearity of the Risk of Infection

we are in the convex part of the curve. For example, to use the case above, a reduction of viral load by 75% for a short exposure could reduce the probability of infection by 95% or more!

Third Error: Mistaking Absence of Evidence for Evidence of Absence

“There is no evidence that masks work”, I kept hearing repeated to me by the usual idiots calling themselves “evidence based” scientists. The point is that there is no evidence that locking the door tonight will prevent me from being burglarized. But everything that may block transmission could help.

We have a) the salon story where two infected stylists failed to infect all their 140 clients (making the probability of infection for bilateral mask wearing safely below 1% for a salon-style exposure)

Fourth Error: Misunderstanding the Market and PeoplePaternalistic bureaucrats resisted inviting the general public to use masks on grounds that the supply was limited and would be needed by health professionals — hence they lied to us saying “masks are not effective”

Fifth Error: Missing Extremely Strong Statistical Signals

they fear to be presenting “anecdotes”, and fail to grasp the broader notion of statistical signals where you look at the whole story, not the body parts.

evidence compounds.

Unlike school, real life is not about certainties. When in doubt, use what protection you can

plus b) the rate of infection of countries where masks were mandatory

plus c) tons of papers with more or less flawed methodologies, etc.

Sixth Error: The Non-Aggression Principle

“Libertarians” (in brackets) are resisting mask wearing on grounds that it constrains their freedom. Yet the entire concept of liberty lies in the Non-Aggression Principle, the equivalent of the Silver Rule: do not harm others; they in turn should not harm you.

Even more insulting is the demand by pseudolibertarians that Costco should banned from forcing customers to wear mask — but libertarianism allows you to set the rules on your own property. Costco should be able to force visitors to wear pink shirts and purple glasses if they wished.

Note that by infecting another person you are not infecting just another person. You are infecting many many more and causing systemic risk.

one of the leading modelers, Gabriela Gomes, suggested the entire area of research was being effectively blackballed out of fear it might encourage a relaxation of pandemic vigilance. “This is the very sad reason for the absence of more optimistic projections on the development of this pandemic in the scientific literature,” she wrote on Twitter. “Our analysis suggests that herd-immunity thresholds are being achieved despite strict social-distancing measures.”

Gomes suggested, herd immunity could happen with as little as one quarter of the population of a community exposed — or perhaps just 20 percent. “We just keep running the models, and it keeps coming back at less than 20 percent,” she told Hamblin. “It’s very striking.” Such findings, if they held up, would be very instructive, as Hamblin writes: “It would mean, for instance, that at 25 percent antibody prevalence, New York City could continue its careful reopening without fear of another major surge in cases.”

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.

In a demonstration of the technology, the team analysed blood from 569 people in the US, South Africa, Thailand and Peru. The test found that, on average, people had been infected with 10 species of viruses, though at least two people in the trial had histories of 84 infections from different kinds of viruses.

The test could bring about major benefits for organ transplant patients. One problem that can follow transplant surgery is the unexpected reawakening of viruses that have lurked inactive in the patient or donor for years. These viruses can return in force when the patient’s immune system is suppressed with drugs to prevent them rejecting the organ. Standard tests often fail to pick up latent viruses before surgery, but the VirScan procedure could reveal their presence and alert doctors and patients to the danger.

The World Mosquito Program (WMP), a nonprofit that pioneered this technique, had run small pilot studies in Australia that suggested it could work. Utarini, who co-leads WMP Yogyakarta, has now shown conclusively that it does.

Carried around the world aboard slave ships, Aedes aegypti has thrived. It is now arguably the most effective human-hunter on the planet, its senses acutely attuned to the carbon dioxide in our breath, the warmth of our bodies, and the odors of our skin.

Wolbachia was first discovered in 1924, in a different species of mosquito. At first, it seemed so unremarkable that scientists ignored it for decades. But starting in the 1980s, they realized that it has an extraordinary knack for spreading. It passes down mainly from insect mothers to their children, and it uses many tricks to ensure that infected individuals are better at reproducing than uninfected ones. To date, it exists in at least 40 percent of all insect species, making it one of the most successful microbes on the planet.

The team divided a large portion of the city into 24 zones and released Wolbachia-infected mosquitoes in half of them. Almost 10,000 volunteers helped distribute egg-filled containers to local backyards. Within a year, about 95 percent of the Aedes mosquitoes in the 12 release zones harbored Wolbachia.

The team found that just 2.3 percent of feverish people who lived in the Wolbachia release zones had dengue, compared with 9.4 percent in the control areas. Wolbachia also seemed to work against all four dengue serotypes, and reduced the number of dengue hospitalizations by 86 percent.

Even then, these already remarkable numbers are likely to be underestimates. The mosquitoes moved around, carrying Wolbachia into the 12 control zones where no mosquitoes were released. And people also move: They might live in a Wolbachia release zone but be bitten and infected with dengue elsewhere. Both of these factors would have worked against the trial, weakening its results

The Wolbachia method does have a few limitations. The bacterium takes months to establish itself, so it can’t be “deployed to contain an outbreak today,” Vazquez-Prokopec told me. As the Yogyakarta trial showed, it works only when Wolbachia reaches a prevalence of at least 80 percent, which requires a lot of work and strong community support

The method has other benefits too. It is self-amplifying and self-perpetuating: If enough Wolbachia-infected mosquitoes are released initially, the bacterium should naturally come to dominate the local population, and stay that way. Unlike insecticides, Wolbachia isn’t toxic, it doesn’t kill beneficial insects (or even mosquitoes), and it doesn’t need to be reapplied, which makes it very cost-effective.

An analysis by Brady’s team showed that it actually saves money by preventing infections

Wolbachia also seems to work against the other diseases that Aedes aegypti carries, including Zika and yellow fever. It could transform this mosquito from one of the most dangerous species to humans into just another biting nuisance.

The new study provides “unassailable” evidence that the central nervous system can control the peripheral immune system, Tracey says. “It’s an incredibly important contribution to the fields of neuroscience and immunology.”

Just as researchers have traced sensory and motor processing to specific brain regions, Tracey suspects that a similar neurological “map” of immunologic information also exists. This new study, he says, is the first direct evidence of that map. “It’s going to be really exciting to see what comes next,” he adds.

it’s unclear whether infectious virus can persist in blood or stool

the infection can spread through the mucous membranes, from the nose down to the rectum.

while the virus appears to zero in on the lungs, it may also be able to infect cells in the gastrointestinal system, experts say. This may be why some patients have symptoms like diarrhea or indigestion

“The virus will actually land on organs like the heart, the kidney, the liver, and may cause some direct damage to those organs,

some patients in China recovered but got sick again, apparently because they had damaged and vulnerable lung tissue that was subsequently attacked by bacteria in their body.

As the body’s immune system shifts into high gear to battle the infection, the resulting inflammation may cause those organs to malfunction, he said.

About 80 percent of people infected with the new coronavirus have relatively mild symptoms. But about 20 percent of people become more seriously ill and in about 2 percent of patients in China, which has had the most cases, the disease has been fatal.

the effects appear to depend on how robust or weakened a person’s immune system is. Older people or those with underlying health issues, like diabetes or another chronic illness, are more likely to develop severe symptoms

the course a patient’s coronavirus will take is not yet fully understood.

Some patients can remain stable for over a week and then suddenly develop pneumonia, Dr. Diaz said. Some patients seem to recover but then develop symptoms again.

more than half of 121 patients in China had normal CT scans early in their disease.

Coronavirus particles have spiked proteins sticking out from their surfaces, and these spikes hook onto cell membranes, allowing the virus’s genetic material to enter the human cell.

That genetic material proceeds to “hijack the metabolism of the cell and say, in effect, ‘Don’t do your usual job. Your job now is to help me multiply and make the virus,’

As copies of the virus multiply, they burst out and infect neighboring cells. The symptoms often start in the back of the throat with a sore throat and a dry cough.

The virus then “crawls progressively down the bronchial tubes,”

That can damage the alveoli or lung sacs and they have to work harder to carry out their function of supplying oxygen to the blood

The swelling and the impaired flow of oxygen can cause those areas in the lungs to fill with fluid, pus and dead cells. Pneumonia, an infection in the lung, can occur

Some people have so much trouble breathing they need to be put on a ventilator

But these latest shifts challenge key infection control assumptions that go back a century, putting a lot of what went wrong last year in context

They may also signal one of the most important advancements in public health during this pandemic.

If the importance of aerosol transmission had been accepted early, we would have been told from the beginning that it was much safer outdoors, where these small particles disperse more easily, as long as you avoid close, prolonged contact with others.

We would have tried to make sure indoor spaces were well ventilated, with air filtered as necessary.

Instead of blanket rules on gatherings, we would have targeted conditions that can produce superspreading events: people in poorly ventilated indoor spaces, especially if engaged over time in activities that increase aerosol production, like shouting and singing

We would have started using masks more quickly, and we would have paid more attention to their fit, too. And we would have been less obsessed with cleaning surfaces.

The implications of this were illustrated when I visited New York City in late April — my first trip there in more than a year.

A giant digital billboard greeted me at Times Square, with the message “Protecting yourself and others from Covid-19. Guidance from the World Health Organization.”

That billboard neglected the clearest epidemiological pattern of this pandemic: The vast majority of transmission has been indoors, sometimes beyond a range of three or even six feet. The superspreading events that play a major role in driving the pandemic occur overwhelmingly, if not exclusively, indoors.

The billboard had not a word about ventilation, nothing about opening windows or moving activities outdoors, where transmission has been rare and usually only during prolonged and close contact. (Ireland recently reported 0.1 percent of Covid-19 cases were traced to outdoor transmission.)

Mary-Louise McLaws, an epidemiologist at the University of New South Wales in Sydney, Australia, and a member of the W.H.O. committees that craft infection prevention and control guidance, wanted all this examined but knew the stakes made it harder to overcome the resistance. She told The Times last year, “If we started revisiting airflow, we would have to be prepared to change a lot of what we do.” She said it was a very good idea, but she added, “It will cause an enormous shudder through the infection control society.”

In contrast, if the aerosols had been considered a major form of transmission, in addition to distancing and masks, advice would have centered on ventilation and airflow, as well as time spent indoors. Small particles can accumulate in enclosed spaces, since they can remain suspended in the air and travel along air currents. This means that indoors, three or even six feet, while helpful, is not completely protective, especially over time.

To see this misunderstanding in action, look at what’s still happening throughout the world. In India, where hospitals have run out of supplemental oxygen and people are dying in the streets, money is being spent on fleets of drones to spray anti-coronavirus disinfectant in outdoor spaces. Parks, beaches and outdoor areas keep getting closed around the world. This year and last, organizers canceled outdoor events for the National Cherry Blossom Festival in Washington, D.C. Cambodian customs officials advised spraying disinfectant outside vehicles imported from India. The examples are many.

Meanwhile, many countries allowed their indoor workplaces to open but with inadequate aerosol protections. There was no attention to ventilation, installing air filters as necessary or even opening windows when possible, more to having people just distancing three or six feet, sometimes not requiring masks beyond that distance, or spending money on hard plastic barriers, which may be useless at best

clear evidence doesn’t easily overturn tradition or overcome entrenched feelings and egos. John Snow, often credited as the first scientific epidemiologist, showed that a contaminated well was responsible for a 1854 London cholera epidemic by removing the suspected pump’s handle and documenting how the cases plummeted afterward. Many other scientists and officials wouldn’t believe him for 12 years, when the link to a water source showed up again and became harder to deny.

Along the way to modern public health shaped largely by the fight over germs, a theory of transmission promoted by the influential public health figure Charles Chapin took hold

Dr. Chapin asserted in the early 1900s that respiratory diseases were most likely spread at close range by people touching bodily fluids or ejecting respiratory droplets, and did not allow for the possibility that such close-range infection could occur by inhaling small floating particles others emitted

He was also concerned that belief in airborne transmission, which he associated with miasma theories, would make people feel helpless and drop their guard against contact transmission. This was a mistake that would haunt infection control for the next century and more.

It was in this context in early 2020 that the W.H.O. and the C.D.C. asserted that SARS-CoV-2 was transmitted primarily via these heavier, short-range droplets, and provided guidance accordingly

Amid the growing evidence, in July, hundreds of scientists signed an open letter urging the public health agencies, especially the W.H.O., to address airborne transmission of the coronavirus.

Last October, the C.D.C. published updated guidance acknowledging airborne transmission, but as a secondary route under some circumstances, until it acknowledged airborne transmission as crucial on Friday. And the W.H.O. kept inching forward in its public statements, most recently a week ago.

Linsey Marr, a professor of engineering at Virginia Tech who made important contributions to our understanding of airborne virus transmission before the pandemic, pointed to two key scientific errors — rooted in a lot of history — that explain the resistance, and also opened a fascinating sociological window into how science can get it wrong and why.

Dr. Marr said that if you inhale a particle from the air, it’s an aerosol.

biomechanically, she said, nasal transmission faces obstacles, since nostrils point downward and the physics of particles that large makes it difficult for them to move up the nose. And in lab measurements, people emit far more of the easier-to-inhale aerosols than the droplets, she said, and even the smallest particles can be virus laden, sometimes more so than the larger ones, seemingly because of how and where they are produced in the respiratory tract.

Second, she said, proximity is conducive to transmission of aerosols as well because aerosols are more concentrated near the person emitting them. In a twist of history, modern scientists have been acting like those who equated stinky air with disease, by equating close contact, a measure of distance, only with the larger droplets, a mechanism of transmission, without examination.

Since aerosols also infect at close range, measures to prevent droplet transmission — masks and distancing — can help dampen transmission for airborne diseases as well. However, this oversight led medical people to circularly assume that if such measures worked at all, droplets must have played a big role in their transmission.

Another dynamic we’ve seen is something that is not unheard-of in the history of science: setting a higher standard of proof for theories that challenge conventional wisdom than for those that support it.

Another key problem is that, understandably, we find it harder to walk things back. It is easier to keep adding exceptions and justifications to a belief than to admit that a challenger has a better explanation.

The ancients believed that all celestial objects revolved around the earth in circular orbits. When it became clear that the observed behavior of the celestial objects did not fit this assumption, those astronomers produced ever-more-complex charts by adding epicycles — intersecting arcs and circles — to fit the heavens to their beliefs.

In a contemporary example of this attitude, the initial public health report on the Mount Vernon choir case said that it may have been caused by people “sitting close to one another, sharing snacks and stacking chairs at the end of the practice,” even though almost 90 percent of the people there developed symptoms of Covid-19

So much of what we have done throughout the pandemic — the excessive hygiene theater and the failure to integrate ventilation and filters into our basic advice — has greatly hampered our response.

Some of it, like the way we underused or even shut down outdoor space, isn’t that different from the 19th-century Londoners who flushed the source of their foul air into the Thames and made the cholera epidemic worse.

Righting this ship cannot be a quiet process — updating a web page here, saying the right thing there. The proclamations that we now know are wrong were so persistent and so loud for so long.

the progress we’ve made might lead to an overhaul in our understanding of many other transmissible respiratory diseases that take a terrible toll around the world each year and could easily cause other pandemics.

So big proclamations require probably even bigger proclamations to correct, or the information void, unnecessary fears and misinformation will persist, damaging the W.H.O. now and in the future.

I’ve seen our paper used in India to try to reason through aerosol transmission and the necessary mitigations. I’ve heard of people in India closing their windows after hearing that the virus is airborne, likely because they were not being told how to respond

The W.H.O. needs to address these fears and concerns, treating it as a matter of profound change, so other public health agencies and governments, as well as ordinary people, can better adjust.

It needs to begin a campaign proportional to the importance of all this, announcing, “We’ve learned more, and here’s what’s changed, and here’s how we can make sure everyone understands how important this is.” That’s what credible leadership looks like. Otherwise, if a web page is updated in the forest without the requisite fanfare, how will it matter?

We have that genetic element that would allow for bacteria that are resistant to every antibiotic.”

colistin

We are one step away from CRE strains that cannot be treated with antibiotics.

overuse of antibiotics in people and in animals put human health at risk by reducing the power of the drugs,

Dr. Krogan and his colleagues set about finding proteins in our cells that the coronavirus uses to grow. Normally, such a project might take two years. But the working group, which includes 22 laboratories, completed it in a few weeks.

In 2011, Dr. Krogan and his colleagues developed a way to find all the human proteins that viruses use to manipulate our cells — a “map,” as Dr. Krogan calls it. They created their first map for H.I.V.

That virus has 18 genes, each of which encodes a protein. The scientists eventually found that H.I.V. interacts, in one way or another, with 435 proteins in a human cell.

In February, the research group synthesized genes from the coronavirus and injected them into cells. They uncovered over 400 human proteins that the virus seems to rely on.

The flulike symptoms observed in infected people are the result of the coronavirus attacking cells in the respiratory tract.

The new map shows that the virus’s proteins travel throughout the human cell, engaging even with proteins that do not seem to have anything to do with making new viruses.

Kevan Shokat, a chemist at U.C.S.F., is poring through 20,000 drugs approved by the Food and Drug Administration for signs that they may interact with the proteins on the map created by Dr. Krogan’s lab.

If promising drugs are found, investigators plan to try them in an animal infected with the coronavirus — perhaps ferrets, because they’re known to get SARS, an illness closely related to Covid-19.

Even if some of these drugs are effective treatments, scientists will still need to make sure they are safe for treating Covid-19. It may turn out, for example, that the dose needed to clear the virus from the body might also lead to dangerous side effects.

In past studies on animals, remdesivir blocked a number of viruses. The drug works by preventing viruses from building new genes.

In February, a team of researchers found that remdesivir could eliminate the coronavirus from infected cells. Since then, five clinical trials have begun to see if the drug will be safe and effective against Covid-19 in people.

Other researchers have taken startling new approaches. On Saturday, Stanford University researchers reported using the gene-editing technology Crispr to destroy coronavirus genes in infected cells.

“Usually by four to six weeks, there’s not much left,” said Deepta Bhattacharya, an immunologist at the University of Arizona. But germinal centers stimulated by the mRNA vaccines are “still going, months into it, and not a lot of decline in most people.”

The broader the range and the longer these cells have to practice, the more likely they are to be able to thwart variants of the virus that may emerge.

“Everyone always focuses on the virus evolving — this is showing that the B cells are doing the same thing,” said Marion Pepper, an immunologist at the University of Washington in Seattle. “And it’s going to be protective against ongoing evolution of the virus, which is really encouraging.”

Dr. Ellebedy’s team found that 15 weeks after the first dose of vaccine, the germinal center was still highly active in all 14 of the participants, and that the number of memory cells that recognized the coronavirus had not declined.

“The fact that the reactions continued for almost four months after vaccination — that’s a very, very good sign,” Dr. Ellebedy said. Germinal centers typically peak one to two weeks after immunization, and then wane.

After an infection or a vaccination, a specialized structure called the germinal center forms in lymph nodes. This structure is an elite school of sorts for B cells — a boot camp where they become increasingly sophisticated and learn to recognize a diverse set of viral genetic sequences.

The results suggest that a vast majority of vaccinated people will be protected over the long term — at least, against the existing coronavirus variants

But older adults, people with weak immune systems and those who take drugs that suppress immunity may need boosters; people who survived Covid-19 and were later immunized may never need them at all.

In the absence of variants that sidestep immunity, in theory immunity could last a lifetime, experts said. But the virus is clearly evolving.

“Anything that would actually require a booster would be variant-based, not based on waning of immunity,” Dr. Bhattacharya said. “I just don’t see that happening.”

The good news: A booster vaccine will probably have the same effect as prior infection in immunized people, Dr. Ellebedy said. “If you give them another chance to engage, they will have a massive response,” he said, referring to memory B cells.

Dr. Ellebedy said the results also suggested that these signs of persistent immune reaction might be caused by mRNA vaccines alone, as opposed to those made by more traditional means, like Johnson & Johnson’s

But that is an unfair comparison, because the Johnson & Johnson vaccine is given as a single dose, Dr. Iwasaki said: “If the J & J had a booster, maybe it will induce this same kind of response.”

a full 64 percent said that even if they tested negative, they would not be comfortable spending time indoors with people they don’t live with.

In an informal survey of 670 epidemiologists, just 6 percent said that if they recently tested negative for the virus, they would be comfortable spending time indoors with others without precautions

“The risk that you have, if everyone is tested before you get together to sit down for dinner, dramatically decreases. It might not ever be zero but, you know, we don’t live in a completely risk-free society.”

Before gathering with others, Dr. Mina said, people could combine a negative test with a two-week quarantine if they’re able

Avoiding any contact with other people for a week or more before taking a test is a powerful tool, said Jeffrey Townsend, a professor of biostatistics at the Yale School of Public Health. Not only does it decrease exposure, but it also gives the virus more opportunity to reach detectable levels in infected people, his research has found.

SEIR models start to fall apart when you think about the underlying causes of the data. You need models that can allow for all possible states, and assess which ones matter for shaping the pandemic’s trajectory over time.

These techniques have enjoyed enormous success ever since they moved out of physics. They’ve been running your iPhone and nuclear power stations for a long time. In my field, neurobiology, we call the approach dynamic causal modelling (DCM). We can’t see brain states directly, but we can infer them given brain imaging data

Epidemiologists currently tackle the inference problem by number-crunching on a huge scale, making use of high-performance computers. Imagine you want to simulate an outbreak in Scotland. Using conventional approaches, this would take you a day or longer with today’s computing resources. And that’s just to simulate one model or hypothesis – one set of parameters and one set of starting conditions.

Using DCM, you can do the same thing in a minute. That allows you to score different hypotheses quickly and easily, and so to home in sooner on the best one.

This is like dark matter in the universe: we can’t see it, but we know it must be there to account for what we can see. Knowing it exists is useful for our preparations for any second wave, because it suggests that targeted testing of those at high risk of exposure to Covid-19 might be a better approach than non-selective testing of the whole population.

Our response as individuals – and as a society – becomes part of the epidemiological process, part of one big self-organising, self-monitoring system. That means it is possible to predict not only numbers of cases and deaths in the future, but also societal and institutional responses – and to attach precise dates to those predictions.

How well have your predictions been borne out in this first wave of infections?For London, we predicted that hospital admissions would peak on 5 April, deaths would peak five days later, and critical care unit occupancy would not exceed capacity – meaning the Nightingale hospitals would not be required. We also predicted that improvements would be seen in the capital by 8 May that might allow social distancing measures to be relaxed – which they were in the prime minister’s announcement on 10 May. To date our predictions have been accurate to within a day or two, so there is a predictive validity to our models that the conventional ones lack.

What do your models say about the risk of a second wave?The models support the idea that what happens in the next few weeks is not going to have a great impact in terms of triggering a rebound – because the population is protected to some extent by immunity acquired during the first wave. The real worry is that a second wave could erupt some months down the line when that immunity wears off.

the important message is that we have a window of opportunity now, to get test-and-trace protocols in place ahead of that putative second wave. If these are implemented coherently, we could potentially defer that wave beyond a time horizon where treatments or a vaccine become available, in a way that we weren’t able to before the first one.

We’ve been comparing the UK and Germany to try to explain the comparatively low fatality rates in Germany. The answers are sometimes counterintuitive. For example, it looks as if the low German fatality rate is not due to their superior testing capacity, but rather to the fact that the average German is less likely to get infected and die than the average Brit. Why? There are various possible explanations, but one that looks increasingly likely is that Germany has more immunological “dark matter” – people who are impervious to infection, perhaps because they are geographically isolated or have some kind of natural resistance

Any other advantages?Yes. With conventional SEIR models, interventions and surveillance are something you add to the model – tweaks or perturbations – so that you can see their effect on morbidity and mortality. But with a generative model these things are built into the model itself, along with everything else that matters.

Are generative models the future of disease modelling?That’s a question for the epidemiologists – they’re the experts. But I would be very surprised if at least some part of the epidemiological community didn’t become more committed to this approach in future, given the impact that Feynman’s ideas have had in so many other disciplines.

Patients in this study had a mean age of 44 years, so were very much part of the young, working-age population. Only 18% had been hospitalised with COVID-19, meaning organ damage may occur even after a non-severe infection.

Another piece of early research (awaiting peer review) suggests that SARS-CoV-2 could also have a long-term impact on people’s organs.

Perhaps unsurprisingly, people with more severe disease initially – characterised by more than five symptoms – seem to be at increased risk of long COVID. Older age and being female also appear to be risk factors for having prolonged symptoms, as is having a higher body mass index.

Rather harder to explore is the symptom of fatigue. Another recent large-scale study has shown that this symptom is common after COVID-19 – occurring in more than half of cases – and appears unrelated to the severity of the early illness.

While men are at increased risk of severe infection, that women seem to be more affected by long COVID may reflect their different or changing hormone status.

Some symptoms of long COVID overlap with menopausal symptoms, and hormone replacement using medication may be one route to reducing the impact of symptoms.

What is clear, however, is that long-term symptoms after COVID-19 are common, and that research into the causes and treatments of long COVID will likely be needed long after the outbreak itself has subsided.