• Vaccination Is Making America Forget a Basic Pandemic Rule - The Atlantic

    Unvaccinated people are not randomly distributed. They tend to cluster together, socially and geographically, enabling the emergence of localized COVID-19 outbreaks. Partly, these clusters exist because vaccine skepticism grows within cultural and political divides, and spreads through social networks. But they also exist because decades of systemic racism have pushed communities of color into poor neighborhoods and low-paying jobs, making it harder for them to access health care in general, and now vaccines in particular.

    As Eleanor Murray, an epidemiologist at Boston University, said on Twitter, “Don’t tell me it’s “safe”; tell me what level of death or disability you are implicitly choosing to accept.” (...) How much additive burden is a country willing to foist upon people who already carry their disproportionate share? What is America’s goal—to end the pandemic, or to suppress it to a level where it mostly plagues communities that privileged individuals can ignore?

  • Three Ways the Pandemic Has Made the World Better - The Atlantic

    par Zeynep Tufekci

    This has been a year of terrible loss. People have lost loved ones to the pandemic. Many have gotten sick, and some are still suffering. Children have lost a year of school. Millions have lost a steady paycheck. Some have lost small businesses that they’d built for decades. Almost all of us have lost hugs and visits and travel and the joy of gathering together at a favorite restaurant and more.

    And yet, this year has also taught us much. Strange as it may sound, the coronavirus pandemic has delivered blessings, and it does not diminish our ongoing suffering to acknowledge them. In fact, recognizing them increases the chance that our society may emerge from this ordeal more capable, more agile, and more prepared for the future.

    Here are three ways the world has changed for the better during this awful year.

    1. We Now Know How to Code for Our Vaccines
    Perhaps the development that will have the most profound implications for future generations is the incredible advances in synthetic messenger RNA (mRNA) biotechnologies.

    But amid all this came historic developments. The new mRNA technology, on which several vaccines—notably Pfizer-BioNTech’s and Moderna’s—are based, is an epochal scientific and technical breakthrough. We are now coding for vaccines, and thanks to advances in science and industrial production, we can mass-produce them and figure out how to deliver them into our cells in a matter of months.

    This is all new. Neither Moderna nor BioNTech had a single approved product on the market before 2020. Each company essentially designed its vaccine on a computer over a weekend in January 2020—BioNTech’s took just a few hours, really. Both companies had vaccine candidates designed at least four weeks before the first confirmed U.S. COVID-19 fatality was announced, and Moderna was producing vaccine batches to be used for its trials more than a month before the World Health Organization declared a pandemic. In 2021, the companies together aim to produce billions of stunningly efficacious vaccine doses,

    The mRNA vaccines work differently. For these, scientists look at the genetic sequence of a virus, identify a crucial part—such as the spike protein, which it uses as a key to bind onto cells’ receptors in order to unlock and enter them—produce instructions to make just that part, and then send those instructions into our cells. After all, that’s what a virus does: It takes over our cells’ machinery to make more of itself. Except in this case, we instruct our cells to make only the spike portion to give our immune system practice with something that cannot infect us—the rest of the virus isn’t there!

    Until this year, that was the dream behind the synthetic mRNA technologies: a dream with few, scattered adherents, uphill battles, and nothing to show for it but promise. This year, it became a reality.

    In 2020, we figured out how to make messenger RNA with precision, by programming the exact code we wanted, producing it at scale (a printing press for messenger RNA!), and figuring out a way to inject it into people so the fragile mRNA makes it into our cells. The first step was pure programming: Uğur Şahin, the CEO of BioNTech, sat at his computer and entered the genetic code of the spike protein of the mysterious virus that had emerged in Wuhan. Moderna employees had done the same thing the weekend after the genomic sequence was released on January 10. The Moderna vaccine candidate was called mRNA-1273 because it encoded all of the 1,273 amino acids in the SARS-CoV-2 spike protein—the code was so small that it could all be represented with little less than half the number of characters that fit on a single-spaced page.

    The rest of the process relied on key scientific and industrial innovations that are quite recent. Messenger RNA are fragile—they disintegrate easily, as they are supposed to. The lipid nanoparticles we envelop them in to use as delivery systems were approved only in 2018. Plus, the viral spike protein is a notorious shape-shifter. It takes one form before it fuses with our cells and another one afterward. The latter, postfusion form did not work well at all for developing vaccines, and scientists only recently figured out how to stabilize a virus’ spike in its prefusion form.

    This may allow us, finally, to transition from a broadcast-only model of medicine, wherein drugs are meant to be identical for everyone in a particular group, to targeted, individualized therapies. Plus, these technologies are suitable for small-scale but cheap-enough production: a development that can help us treat rare diseases that afflict only a few thousand people each year, and are thus usually ignored by mass-market-oriented medical technologies.

    It’s also no coincidence that these two mRNA vaccines were the fastest to market. They can be manufactured rapidly and, crucially, updated blazingly fast. Şahin, the BioNTech CEO, estimates that six weeks is enough time for the company to start producing new boosters for whenever a new COVID-19 variant emerges. Pfizer and Moderna are both already working on boosters that better target the new variants we’ve seen so far, and the FDA has said it can approve these tweaks quickly.
    2. We Actually Learned How to Use Our Digital Infrastructure
    The internet, widespread digital connectivity, our many apps—it’s easy to forget how new most of this is. Zoom, the ubiquitous video service that became synonymous with pandemic work, and that so many of us are understandably a little sick of, is less than 10 years old. Same with the kind of broadband access that allowed billions to stream entertainment at home and keep in touch with family members and colleagues. Internet connectivity is far from perfect or equally distributed, but it has gotten faster and more expansive over the past decade; without it, the pandemic would have been much more miserable and costly.

    Technology also showed how we could make our society function better in normal times.

    According to the CDC, telehealth visits increased by 50 percent in the first quarter of 2020, compared with the same period in 2019. Such visits are clearly not appropriate for every condition, but when warranted, they can make it much easier for people to access medical help without worrying about transportation, child care, or excessive time away from work. Remote access to medical help has long been a request from people with disabilities and people in rural areas, for whom traveling to clinics can be an extra burden.

    Work, too, has been transformed. Suddenly, hundreds of millions of people around the world had to figure out how to get things done without going into the office. It turns out that for many white-collar jobs, this is not just possible; it comes with a variety of upsides.

    3. We’ve Unleashed the True Spirit of Peer Review and Open Science

    On January 10, 2020, an Australian virologist, Edward Holmes, published a modest tweet: “All, an initial genome sequence of the coronavirus associated with the Wuhan outbreak is now available at Virological.org here.” A microbiologist responded with “And so it begins!” and added a GIF of planes taking off. And so it did indeed begin: a remarkable year of open, rapid, collaborative, dynamic—and, yes, messy—scientific activity, which included ways of collaborating that would have been unthinkable even a few decades ago.

    Well, no more. When the pandemic hit, it simply wasn’t tenable to keep playing the old, slow, closed game, and the scientific community let loose. Peer review—the real thing, not just the formal version locked up by for-profit companies—broke out of its constraints. A good deal of the research community started publishing its findings as “preprints”—basically, papers before they get approved by formal publications—placing them in nonprofit scientific depositories that had no paywalls. The preprints were then fiercely and openly debated—often on social media, which is not necessarily the ideal place for it, but that’s what we had. Sometimes, the release of data was even faster: Some of the most important initial data about the immune response to the worrisome U.K. variant came from a Twitter thread by a tired but generous researcher in Texas. It showed true scientific spirit: The researcher’s lab was eschewing the prestige of being first to publish results in a manuscript by allowing others to get to work as fast as possible. The papers often also went through the formal peer review as well, eventually getting published in a journal, but the pandemic has forced many of these companies to drop their paywalls—besides, the preprints on which the final papers are based remain available to everyone.

    Working together, too, has expanded in ways that were hard to imagine without the new digital tools that allow for rapid sharing and collaboration, and also the sense of urgency that broke through disciplinary silos.

    The pandemic happened at a moment of convergence for medical and digital technology and social dynamics, which revealed enormous positive potential for people. Nothing will erase the losses we experienced. But this awful year has nudged us toward dramatic improvements in human life, thanks to new biotechnologies, greater experience with the positive aspects of digital connectivity, and a more dynamic scientific process.

    #Zeynep_Tufekci #Pandémie #Changement_social

  • Where the Pandemic Will Take America in 2021 - The Atlantic

    Vietnam, the first country to contain SARS in 2003, “immediately understood that a few cases without an emergency-level response will be thousands of cases in a short period,” said Lincoln, the San Francisco State medical anthropologist, who has worked in Vietnam extensively. “Their public-health response was just impeccable and relentless, and the public supports health agencies.” At the time of my writing, Vietnam had recorded just 1,451 cases of COVID-19 all year, fewer than each of the 32 hardest-hit U.S. prisons.

    Rwanda also took the pandemic seriously from the start. It instituted a strict lockdown after its first case, in March; mandated masks a month later; offered tests frequently and freely; and provided food and space to people who had to quarantine. Though ranked 117th in preparedness, and with only 1 percent of America’s per capita GDP, Rwanda has recorded just 8,021 cases of COVID-19 and 75 deaths in total. For comparison, the disease has killed more Americans, on average, every hour of December.

    (Pour le Rwanda, PIH, l’association de #Paul_Farmer, n’y est pas pour rien)

    “We are too focused on high-tech and expensive health care. We’re set up to fail in a pandemic like this.”

    After the post-9/11 anthrax attacks in 2001, fears of bioterrorism encroached on American attitudes toward naturally emerging diseases. Preparedness was framed with the rhetoric of national security. Health experts developed surveillance systems for disease, simulated epidemics in war games, and focused on fighting outbreaks in other countries. “This came at the expense of investment in public health, equity, and housing—boringly crucial sectors that actually support human wellness,”

    approches sécuritaires ou sanitaires de la #santé

    “One cannot prevent a pandemic by preparing for a war, but that is exactly what the U.S. has been doing.”

    et dans l’article suivant, cité par Ed Yong, un remarquable graphique de l’absence totale de corrélation entre les critères habituels d’évaluation des systèmes de santé et l’impact du COVID-19.

  • « This Overlooked Variable Is the Key to the Pandemic — It’s not R. » by Zeynep Tufekci, 30.09.2020

    « In an overdispersed regime, identifying transmission events (someone infected someone else) is more important than identifying infected individuals.

    » […] If we can use retrospective contact tracing to find the person who infected our patient, and then trace the forward contacts of the infecting person, we are generally going to find a lot more cases compared with forward-tracing contacts of the infected patient, which will merely identify potential exposures, many of which will not happen anyway, because most transmission chains die out on their own. »

    » […] Indeed, as Kucharski and his co-authors show mathematically, overdispersion means that “forward tracing alone can, on average, identify at most the mean number of secondary infections (i.e. R)”; in contrast, “backward tracing increases this maximum number of traceable individuals by a factor of 2-3, as index cases are more likely to come from clusters than a case is to generate a cluster.” »

    » […] Even in an overdispersed pandemic, it’s not pointless to do forward tracing to be able to warn and test people, if there are extra resources and testing capacity. But it doesn’t make sense to do forward tracing while not devoting enough resources to backward tracing and finding clusters, which cause so much damage. »

    » […] Oshitani said he believes that “the chain of transmission cannot be sustained without a chain of clusters or a megacluster.” Japan thus carried out a cluster-busting approach, including undertaking aggressive backward tracing to uncover clusters. Japan also focused on ventilation, counseling its population to avoid places where the three C’s come together—crowds in closed spaces in close contact, especially if there’s talking or singing—bringing together the science of overdispersion with the recognition of airborne aerosol transmission, as well as presymptomatic and asymptomatic transmission. »

    #covid19 #contactTracing #graphs

  • K : The Overlooked Variable That’s Driving the Pandemic - The Atlantic

    There’s something strange about this #coronavirus #pandemic. Even after months of extensive research by the global scientific community, many questions remain open.

    Why, for instance, was there such an enormous death toll in northern Italy, but not the rest of the country? Just three contiguous regions in northern Italy have 25,000 of the country’s nearly 36,000 total deaths; just one region, Lombardy, has about 17,000 deaths. Almost all of these were concentrated in the first few months of the outbreak. What happened in Guayaquil, Ecuador, in April, when so many died so quickly that bodies were abandoned in the sidewalks and streets?* Why, in the spring of 2020, did so few cities account for a substantial portion of global deaths, while many others with similar density, weather, age distribution, and travel patterns were spared? What can we really learn from Sweden, hailed as a great success by some because of its low case counts and deaths as the rest of Europe experiences a second wave, and as a big failure by others because it did not lock down and suffered excessive death rates earlier in the pandemic? Why did widespread predictions of catastrophe in Japan not bear out? The baffling examples go on.

    I’ve heard many explanations for these widely differing trajectories over the past nine months—weather, elderly populations, vitamin D, prior immunity, herd immunity—but none of them explains the timing or the scale of these drastic variations. But there is a potential, overlooked way of understanding this pandemic that would help answer these questions, reshuffle many of the current heated arguments, and, crucially, help us get the spread of COVID-19 under control.

    By now many people have heard about R0—the basic reproductive number of a pathogen, a measure of its contagiousness on average. But unless you’ve been reading scientific journals, you’re less likely to have encountered k, the measure of its dispersion. The definition of k is a mouthful, but it’s simply a way of asking whether a virus spreads in a steady manner or in big bursts, whereby one person infects many, all at once. After nine months of collecting epidemiological data, we know that this is an overdispersed pathogen, meaning that it tends to spread in clusters, but this knowledge has not yet fully entered our way of thinking about the pandemic—or our preventive practices.

    The now-famed R0 (pronounced as “r-naught”) is an average measure of a pathogen’s contagiousness, or the mean number of susceptible people expected to become infected after being exposed to a person with the disease. If one ill person infects three others on average, the R0 is three. This parameter has been widely touted as a key factor in understanding how the pandemic operates. News media have produced multiple explainers and visualizations for it. Movies praised for their scientific accuracy on pandemics are lauded for having characters explain the “all-important” R0. Dashboards track its real-time evolution, often referred to as R or Rt, in response to our interventions. (If people are masking and isolating or immunity is rising, a disease can’t spread the same way anymore, hence the difference between R0 and R.)

    Unfortunately, averages aren’t always useful for understanding the distribution of a phenomenon, especially if it has widely varying behavior. If Amazon’s CEO, Jeff Bezos, walks into a bar with 100 regular people in it, the average wealth in that bar suddenly exceeds $1 billion. If I also walk into that bar, not much will change. Clearly, the average is not that useful a number to understand the distribution of wealth in that bar, or how to change it. Sometimes, the mean is not the message. Meanwhile, if the bar has a person infected with COVID-19, and if it is also poorly ventilated and loud, causing people to speak loudly at close range, almost everyone in the room could potentially be infected—a pattern that’s been observed many times since the pandemic begin, and that is similarly not captured by R. That’s where the dispersion comes in.

    There are COVID-19 incidents in which a single person likely infected 80 percent or more of the people in the room in just a few hours. But, at other times, COVID-19 can be surprisingly much less contagious. Overdispersion and super-spreading of this virus are found in research across the globe. A growing number of studies estimate that a majority of infected people may not infect a single other person. A recent paper found that in Hong Kong, which had extensive testing and contact tracing, about 19 percent of cases were responsible for 80 percent of transmission, while 69 percent of cases did not infect another person. This finding is not rare: Multiple studies from the beginning have suggested that as few as 10 to 20 percent of infected people may be responsible for as much as 80 to 90 percent of transmission, and that many people barely transmit it.

    This highly skewed, imbalanced distribution means that an early run of bad luck with a few super-spreading events, or clusters, can produce dramatically different outcomes even for otherwise similar countries. Scientists looked globally at known early-introduction events, in which an infected person comes into a country, and found that in some places, such imported cases led to no deaths or known infections, while in others, they sparked sizable outbreaks. Using genomic analysis, researchers in New Zealand looked at more than half the confirmed cases in the country and found a staggering 277 separate introductions in the early months, but also that only 19 percent of introductions led to more than one additional case. A recent review shows that this may even be true in congregate living spaces, such as nursing homes, and that multiple introductions may be necessary before an outbreak takes off. Meanwhile, in Daegu, South Korea, just one woman, dubbed Patient 31, generated more than 5,000 known cases in a megachurch cluster.

    Unsurprisingly, SARS-CoV, the previous incarnation of SARS-CoV-2 that caused the 2003 SARS outbreak, was also overdispersed in this way: The majority of infected people did not transmit it, but a few super-spreading events caused most of the outbreaks. MERS, another coronavirus cousin of SARS, also appears overdispersed, but luckily, it does not—yet—transmit well among humans.

    This kind of behavior, alternating between being super infectious and fairly noninfectious, is exactly what k captures, and what focusing solely on R hides. Samuel Scarpino, an assistant professor of epidemiology and complex systems at Northeastern, told me that this has been a huge challenge, especially for health authorities in Western societies, where the pandemic playbook was geared toward the flu—and not without reason, because pandemic flu is a genuine threat. However, influenza does not have the same level of clustering behavior.

    We can think of disease patterns as leaning deterministic or stochastic: In the former, an outbreak’s distribution is more linear and predictable; in the latter, randomness plays a much larger role and predictions are hard, if not impossible, to make. In deterministic trajectories, we expect what happened yesterday to give us a good sense of what to expect tomorrow. Stochastic phenomena, however, don’t operate like that—the same inputs don’t always produce the same outputs, and things can tip over quickly from one state to the other. As Scarpino told me, “Diseases like the flu are pretty nearly deterministic and R0 (while flawed) paints about the right picture (nearly impossible to stop until there’s a vaccine).” That’s not necessarily the case with super-spreading diseases.

    Nature and society are replete with such imbalanced phenomena, some of which are said to work according to the Pareto principle, named after the sociologist Vilfredo Pareto. Pareto’s insight is sometimes called the 80/20 principle—80 percent of outcomes of interest are caused by 20 percent of inputs—though the numbers don’t have to be that strict. Rather, the Pareto principle means that a small number of events or people are responsible for the majority of consequences. This will come as no surprise to anyone who has worked in the service sector, for example, where a small group of problem customers can create almost all the extra work. In cases like those, booting just those customers from the business or giving them a hefty discount may solve the problem, but if the complaints are evenly distributed, different strategies will be necessary. Similarly, focusing on the R alone, or using a flu-pandemic playbook, won’t necessarily work well for an overdispersed pandemic.

    Hitoshi Oshitani, a member of the National COVID-19 Cluster Taskforce at Japan’s Ministry of Health, Labour and Welfare and a professor at Tohoku University who told me that Japan focused on the overdispersion impact from early on, likens his country’s approach to looking at a forest and trying to find the clusters, not the trees. Meanwhile, he believes, the Western world was getting distracted by the trees, and got lost among them. To fight a super-spreading disease effectively, policy makers need to figure out why super-spreading happens, and they need to understand how it affects everything, including our contact-tracing methods and our testing regimes.

    There may be many different reasons a pathogen super-spreads. Yellow fever spreads mainly via the mosquito Aedes aegypti, but until the insect’s role was discovered, its transmission pattern bedeviled many scientists. Tuberculosis was thought to be spread by close-range droplets until an ingenious set of experiments proved that it was airborne. Much is still unknown about the super-spreading of SARS-CoV-2. It might be that some people are super-emitters of the virus, in that they spread it a lot more than other people. Like other diseases, contact patterns surely play a part: A politician on the campaign trail or a student in a college dorm is very different in how many people they could potentially expose compared with, say, an elderly person living in a small household. However, looking at nine months of epidemiological data, we have important clues to some of the factors.

    In study after study, we see that super-spreading clusters of COVID-19 almost overwhelmingly occur in poorly ventilated, indoor environments where many people congregate over time—weddings, churches, choirs, gyms, funerals, restaurants, and such—especially when there is loud talking or singing without masks. For super-spreading events to occur, multiple things have to be happening at the same time, and the risk is not equal in every setting and activity, Muge Cevik, a clinical lecturer in infectious diseases and medical virology at the University of St. Andrews and a co-author of a recent extensive review of transmission conditions for COVID-19, told me.

    Cevik identifies “prolonged contact, poor ventilation, [a] highly infectious person, [and] crowding” as the key elements for a super-spreader event. Super-spreading can also occur indoors beyond the six-feet guideline, because SARS-CoV-2, the pathogen causing COVID-19, can travel through the air and accumulate, especially if ventilation is poor. Given that some people infect others before they show symptoms, or when they have very mild or even no symptoms, it’s not always possible to know if we are highly infectious ourselves. We don’t even know if there are more factors yet to be discovered that influence super-spreading. But we don’t need to know all the sufficient factors that go into a super-spreading event to avoid what seems to be a necessary condition most of the time: many people, especially in a poorly ventilated indoor setting, and especially not wearing masks. As Natalie Dean, a biostatistician at the University of Florida, told me, given the huge numbers associated with these clusters, targeting them would be very effective in getting our transmission numbers down.

    Overdispersion should also inform our contact-tracing efforts. In fact, we may need to turn them upside down. Right now, many states and nations engage in what is called forward or prospective contact tracing. Once an infected person is identified, we try to find out with whom they interacted afterward so that we can warn, test, isolate, and quarantine these potential exposures. But that’s not the only way to trace contacts. And, because of overdispersion, it’s not necessarily where the most bang for the buck lies. Instead, in many cases, we should try to work backwards to see who first infected the subject.

    Because of overdispersion, most people will have been infected by someone who also infected other people, because only a small percentage of people infect many at a time, whereas most infect zero or maybe one person. As Adam Kucharski, an epidemiologist and the author of the book The Rules of Contagion, explained to me, if we can use retrospective contact tracing to find the person who infected our patient, and then trace the forward contacts of the infecting person, we are generally going to find a lot more cases compared with forward-tracing contacts of the infected patient, which will merely identify potential exposures, many of which will not happen anyway, because most transmission chains die out on their own.

    The reason for backward tracing’s importance is similar to what the sociologist Scott L. Feld called the friendship paradox: Your friends are, on average, going to have more friends than you. (Sorry!) It’s straightforward once you take the network-level view. Friendships are not distributed equally; some people have a lot of friends, and your friend circle is more likely to include those social butterflies, because how could it not? They friended you and others. And those social butterflies will drive up the average number of friends that your friends have compared with you, a regular person. (Of course, this will not hold for the social butterflies themselves, but overdispersion means that there are much fewer of them.) Similarly, the infectious person who is transmitting the disease is like the pandemic social butterfly: The average number of people they infect will be much higher than most of the population, who will transmit the disease much less frequently. Indeed, as Kucharski and his co-authors show mathematically, overdispersion means that “forward tracing alone can, on average, identify at most the mean number of secondary infections (i.e. R)”; in contrast, “backward tracing increases this maximum number of traceable individuals by a factor of 2-3, as index cases are more likely to come from clusters than a case is to generate a cluster.”

    Even in an overdispersed pandemic, it’s not pointless to do forward tracing to be able to warn and test people, if there are extra resources and testing capacity. But it doesn’t make sense to do forward tracing while not devoting enough resources to backward tracing and finding clusters, which cause so much damage.

    Another significant consequence of overdispersion is that it highlights the importance of certain kinds of rapid, cheap tests. Consider the current dominant model of test and trace. In many places, health authorities try to trace and find forward contacts of an infected person: everyone they were in touch with since getting infected. They then try to test all of them with expensive, slow, but highly accurate PCR (polymerase chain reaction) tests. But that’s not necessarily the best way when clusters are so important in spreading the disease.

    PCR tests identify RNA segments of the coronavirus in samples from nasal swabs—like looking for its signature. Such diagnostic tests are measured on two different dimensions: Are they good at identifying people who are not infected (specificity), and are they good at identifying people who are infected (sensitivity)? PCR tests are highly accurate for both dimensions. However, PCR tests are also slow and expensive, and they require a long, uncomfortable swab up the nose at a medical facility. The slow processing times means that people don’t get timely information when they need it. Worse, PCR tests are so responsive that they can find tiny remnants of coronavirus signatures long after someone has stopped being contagious, which can cause unnecessary quarantines.

    Meanwhile, researchers have shown that rapid tests that are very accurate for identifying people who do not have the disease, but not as good at identifying infected individuals, can help us contain this pandemic. As Dylan Morris, a doctoral candidate in ecology and evolutionary biology at Princeton, told me, cheap, low-sensitivity tests can help mitigate a pandemic even if it is not overdispersed, but they are particularly valuable for cluster identification during an overdispersed one. This is especially helpful because some of these tests can be administered via saliva and other less-invasive methods, and be distributed outside medical facilities.

    In an overdispersed regime, identifying transmission events (someone infected someone else) is more important than identifying infected individuals. Consider an infected person and their 20 forward contacts—people they met since they got infected. Let’s say we test 10 of them with a cheap, rapid test and get our results back in an hour or two. This isn’t a great way to determine exactly who is sick out of that 10, because our test will miss some positives, but that’s fine for our purposes. If everyone is negative, we can act as if nobody is infected, because the test is pretty good at finding negatives. However, the moment we find a few transmissions, we know we may have a super-spreader event, and we can tell all 20 people to assume they are positive and to self-isolate—if there are one or two transmissions, there are likely more, exactly because of the clustering behavior. Depending on age and other factors, we can test those people individually using PCR tests, which can pinpoint who is infected, or ask them all to wait it out.

    Scarpino told me that overdispersion also enhances the utility of other aggregate methods, such as wastewater testing, especially in congregate settings like dorms or nursing homes, allowing us to detect clusters without testing everyone. Wastewater testing also has low sensitivity; it may miss positives if too few people are infected, but that’s fine for population-screening purposes. If the wastewater testing is signaling that there are likely no infections, we do not need to test everyone to find every last potential case. However, the moment we see signs of a cluster, we can rapidly isolate everyone, again while awaiting further individualized testing via PCR tests, depending on the situation.

    Unfortunately, until recently, many such cheap tests had been held up by regulatory agencies in the United States, partly because they were concerned with their relative lack of accuracy in identifying positive cases compared with PCR tests—a worry that missed their population-level usefulness for this particular overdispersed pathogen.

    To return to the mysteries of this pandemic, what did happen early on to cause such drastically different trajectories in otherwise similar places? Why haven’t our usual analytic tools—case studies, multi-country comparisons—given us better answers? It’s not intellectually satisfying, but because of the overdispersion and its stochasticity, there may not be an explanation beyond that the worst-hit regions, at least initially, simply had a few unlucky early super-spreading events. It wasn’t just pure luck: Dense populations, older citizens, and congregate living, for example, made cities around the world more susceptible to outbreaks compared with rural, less dense places and those with younger populations, less mass transit, or healthier citizenry. But why Daegu in February and not Seoul, despite the two cities being in the same country, under the same government, people, weather, and more? As frustrating at it may be, sometimes, the answer is merely where Patient 31 and the megachurch she attended happened to be.

    Overdispersion makes it harder for us to absorb lessons from the world, because it interferes with how we ordinarily think about cause and effect. For example, it means that events that result in spreading and non-spreading of the virus are asymmetric in their ability to inform us. Take the highly publicized case in Springfield, Missouri, in which two infected hairstylists, both of whom wore masks, continued to work with clients while symptomatic. It turns out that no apparent infections were found among the 139 exposed clients (67 were directly tested; the rest did not report getting sick). While there is a lot of evidence that masks are crucial in dampening transmission, that event alone wouldn’t tell us if masks work. In contrast, studying transmission, the rarer event, can be quite informative. Had those two hairstylists transmitted the virus to large numbers of people despite everyone wearing masks, it would be important evidence that, perhaps, masks aren’t useful in preventing super-spreading.

    Comparisons, too, give us less information compared with phenomena for which input and output are more tightly coupled. When that’s the case, we can check for the presence of a factor (say, sunshine or Vitamin D) and see if it correlates with a consequence (infection rate). But that’s much harder when the consequence can vary widely depending on a few strokes of luck, the way that the wrong person was in the wrong place sometime in mid-February in South Korea. That’s one reason multi-country comparisons have struggled to identify dynamics that sufficiently explain the trajectories of different places.

    Once we recognize super-spreading as a key lever, countries that look as if they were too relaxed in some aspects appear very different, and our usual polarized debates about the pandemic are scrambled, too. Take Sweden, an alleged example of the great success or the terrible failure of herd immunity without lockdowns, depending on whom you ask. In reality, although Sweden joins many other countries in failing to protect elderly populations in congregate-living facilities, its measures that target super-spreading have been stricter than many other European countries. Although it did not have a complete lockdown, as Kucharski pointed out to me, Sweden imposed a 50-person limit on indoor gatherings in March, and did not remove the cap even as many other European countries eased such restrictions after beating back the first wave. (Many are once again restricting gathering sizes after seeing a resurgence.) Plus, the country has a small household size and fewer multigenerational households compared with most of Europe, which further limits transmission and cluster possibilities. It kept schools fully open without distancing or masks, but only for children under 16, who are unlikely to be super-spreaders of this disease. Both transmission and illness risks go up with age, and Sweden went all online for higher-risk high-school and university students—the opposite of what we did in the United States. It also encouraged social-distancing, and closed down indoor places that failed to observe the rules. From an overdispersion and super-spreading point of view, Sweden would not necessarily be classified as among the most lax countries, but nor is it the most strict. It simply doesn’t deserve this oversize place in our debates assessing different strategies.

    Although overdispersion makes some usual methods of studying causal connections harder, we can study failures to understand which conditions turn bad luck into catastrophes. We can also study sustained success, because bad luck will eventually hit everyone, and the response matters.

    The most informative case studies may well be those who had terrible luck initially, like South Korea, and yet managed to bring about significant suppression. In contrast, Europe was widely praised for its opening early on, but that was premature; many countries there are now experiencing widespread rises in cases and look similar to the United States in some measures. In fact, Europe’s achieving a measure of success this summer and relaxing, including opening up indoor events with larger numbers, is instructive in another important aspect of managing an overdispersed pathogen: Compared with a steadier regime, success in a stochastic scenario can be more fragile than it looks.

    Once a country has too many outbreaks, it’s almost as if the pandemic switches into “flu mode,” as Scarpino put it, meaning high, sustained levels of community spread even though a majority of infected people may not be transmitting onward. Scarpino explained that barring truly drastic measures, once in that widespread and elevated mode, COVID-19 can keep spreading because of the sheer number of chains already out there. Plus, the overwhelming numbers may eventually spark more clusters, further worsening the situation.

    As Kucharski put it, a relatively quiet period can hide how quickly things can tip over into large outbreaks and how a few chained amplification events can rapidly turn a seemingly under-control situation into a disaster. We’re often told that if Rt, the real-time measure of the average spread, is above one, the pandemic is growing, and that below one, it’s dying out. That may be true for an epidemic that is not overdispersed, and while an Rt below one is certainly good, it’s misleading to take too much comfort from a low Rt when just a few events can reignite massive numbers. No country should forget South Korea’s Patient 31.

    That said, overdispersion is also a cause for hope, as South Korea’s aggressive and successful response to that outbreak—with a massive testing, tracing, and isolating regime—shows. Since then, South Korea has also been practicing sustained vigilance, and has demonstrated the importance of backward tracing. When a series of clusters linked to nightclubs broke out in Seoul recently, health authorities aggressively traced and tested tens of thousands of people linked to the venues, regardless of their interactions with the index case, six feet apart or not—a sensible response, given that we know the pathogen is airborne.

    Perhaps one of the most interesting cases has been Japan, a country with middling luck that got hit early on and followed what appeared to be an unconventional model, not deploying mass testing and never fully shutting down. By the end of March, influential economists were publishing reports with dire warnings, predicting overloads in the hospital system and huge spikes in deaths. The predicted catastrophe never came to be, however, and although the country faced some future waves, there was never a large spike in deaths despite its aging population, uninterrupted use of mass transportation, dense cities, and lack of a formal lockdown.

    It’s not that Japan was better situated than the United States in the beginning. Similar to the U.S. and Europe, Oshitani told me, Japan did not initially have the PCR capacity to do widespread testing. Nor could it impose a full lockdown or strict stay-at-home orders; even if that had been desirable, it would not have been legally possible in Japan.

    Oshitani told me that in Japan, they had noticed the overdispersion characteristics of COVID-19 as early as February, and thus created a strategy focusing mostly on cluster-busting, which tries to prevent one cluster from igniting another. Oshitani said he believes that “the chain of transmission cannot be sustained without a chain of clusters or a megacluster.” Japan thus carried out a cluster-busting approach, including undertaking aggressive backward tracing to uncover clusters. Japan also focused on ventilation, counseling its population to avoid places where the three C’s come together—crowds in closed spaces in close contact, especially if there’s talking or singing—bringing together the science of overdispersion with the recognition of airborne aerosol transmission, as well as presymptomatic and asymptomatic transmission.

    Oshitani contrasts the Japanese strategy, nailing almost every important feature of the pandemic early on, with the Western response, trying to eliminate the disease “one by one” when that’s not necessarily the main way it spreads. Indeed, Japan got its cases down, but kept up its vigilance: When the government started noticing an uptick in community cases, it initiated a state of emergency in April and tried hard to incentivize the kinds of businesses that could lead to super-spreading events, such as theaters, music venues, and sports stadiums, to close down temporarily. Now schools are back in session in person, and even stadiums are open—but without chanting.

    It’s not always the restrictiveness of the rules, but whether they target the right dangers. As Morris put it, “Japan’s commitment to ‘cluster-busting’ allowed it to achieve impressive mitigation with judiciously chosen restrictions. Countries that have ignored super-spreading have risked getting the worst of both worlds: burdensome restrictions that fail to achieve substantial mitigation. The U.K.’s recent decision to limit outdoor gatherings to six people while allowing pubs and bars to remain open is just one of many such examples.”

    Could we get back to a much more normal life by focusing on limiting the conditions for super-spreading events, aggressively engaging in cluster-busting, and deploying cheap, rapid mass tests—that is, once we get our case numbers down to low enough numbers to carry out such a strategy? (Many places with low community transmission could start immediately.) Once we look for and see the forest, it becomes easier to find our way out.

  • Covid et immunité : des pistes négligées ? - Page 1 | Mediapart

    Des études signalent une diminution rapide des anticorps après une infection, et plusieurs cas de réinfection ont été rapportés cet été. Que sait-on aujourd’hui de notre immunité ? Dans la recherche de vaccins, une vision tronquée ne risque-t-elle pas de nous fourvoyer ?

    Commençons d’abord par les bonnes nouvelles : les études montrent que plus de 90 % des personnes contaminées par le virus produisent des anticorps dirigés spécifiquement contre le virus, qu’elles aient développé ou non des symptômes. Et ce, même chez les octogénaires https://doi.org/d7p2. En outre, lorsqu’ils sont étudiés en laboratoire, ces anticorps possèdent un fort pouvoir neutralisant : même à faible dose, ils parviennent à éviter que les cellules en culture soient infectées.

    Passons maintenant aux mauvaises nouvelles : ces anticorps ont tendance à disparaître rapidement. Et leur diminution est d’autant plus forte et rapide que les symptômes ont été légers ou inaperçus. Une étude https://www.nature.com/articles/s41591-020-0965-6 publiée dans Nature Medicine portant sur plus de 200 personnes contaminées en Chine révèle qu’au bout de huit semaines, ils sont à des niveaux indétectables pour 40 % des sujets asymptomatiques et 18 % des sujets symptomatiques.

    Autre mauvaise nouvelle estivale : plusieurs cas de réinfection commencent à être rapportés, comme cet homme de Hong Kong https://pubmed.ncbi.nlm.nih.gov/32840608 dont l’analyse génétique du virus a permis d’affirmer qu’il s’agissait bien d’une réinfection et non d’une infection persistante. Notre immunité pourrait-elle disparaître en quelques mois ? Peut-on – oui ou non – compter sur notre système immunitaire pour nous protéger d’une deuxième vague ?

    En réalité, au fur et à mesure des publications, un constat s’impose : les tests immunitaires classiques ne nous offrent qu’une fenêtre très limitée sur la réalité de notre réponse au virus. Un peu comme si l’on regardait par le trou de la serrure une pièce de théâtre : il y a des dizaines d’acteurs répartis sur la scène, mais nous n’en voyons que quelques-uns interagir. Ce sont les fameux anticorps dits IgM et IgG mesurés lors des tests sanguins. Or, non seulement tout ne se passe pas dans le sang, mais ces acteurs ne sont pas, tant s’en faut, les seuls héros de cette lutte intérieure.

    Et si l’on abandonnait le trou de serrure pour une place en tribune ? Prêts ? Ouverture des rideaux.

    Premier décor : le nez. Cette péninsule chère à Cyrano de Bergerac semble en effet être l’endroit du corps qui compte le plus de récepteurs ACE2 (pour Angiotensin Converting Enzyme 2), la fameuse porte d’entrée du virus, celle qui lui permet de pénétrer à l’intérieur des cellules pour s’y multiplier (voir notre article sur ce point). C’est donc ici que commence notre bataille contre le SARS-CoV-2.

    À peine engluées dans notre mucus nasal, les minuscules particules virales couronnées de pics (d’où le nom de coronavirus) sont repérées par nos cellules phagocytaires – littéralement « mangeuses de cellules » – qui se trouvent sur place. Celles-ci se mettent à boulotter un à un ces éléments étrangers, tout en déclenchant la production de molécules chimiques, dont les fameuses cytokines, également capables d’attaquer ces indésirables. C’est ce qu’on appelle l’immunité innée. Avec un peu de chance, l’infection peut tourner court dès cette étape et ne jamais sortir du mucus nasal ou respiratoire. C’est probablement ce qui se passe chez la plupart des enfants, fréquemment exposés aux infections respiratoires, estiment certains chercheurs https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221011. Mais à mesure que l’on vieillit, cette première ligne de défense se laisse vite déborder.

    D’autant plus que ce virus semble avoir acquis une astuce pour mieux survivre dans notre nez : lorsqu’il s’y trouve en grande quantité, il parvient à inhiber cette réponse immédiate pendant un jour ou deux. D’après Akiko Iwasaki https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255347, immunologiste à l’université de Yale, cette capacité d’inhiber nos défenses innées serait l’un des déterminants du succès du SARS-CoV-2. Elle offre une petite fenêtre de temps supplémentaire durant laquelle le virus en profite pour se répliquer silencieusement. Avant qu’une autre ligne de défense ne se mette en place, l’acte II de notre pièce de théâtre : l’immunité dite adaptative.

    Généralement, on mesure cette immunité à la quantité d’anticorps capables de neutraliser le virus dans le sang. Dans la plupart des analyses sérologiques, deux types d’anticorps sont quantifiés : les IgM, qui apparaissent dès le 3e jour suivant l’infection, et les IgG, détectés généralement à partir du 14e jour. Sauf que dans la vraie vie, bien d’autres acteurs entrent en jeu dans cette seconde étape de la bataille.

    Restons dans nos muqueuses respiratoires. Après tout, c’est là que le virus commence son invasion. Durant le festin initial de nos cellules phagocytaires, des morceaux de virus (en particulier les protéines situées sur l’enveloppe du virus, appelées antigènes) sont récupérés et présentés à nos « agents spéciaux » : les lymphocytes. Parmi eux, les lymphocytes B se mettent alors à se multiplier à toute allure, faisant d’ailleurs grossir nos ganglions lymphatiques. Par une succession de hasards, de mutations génétiques et de cassures, certains de ces lymphocytes finissent par obtenir un récepteur capable de reconnaître et de se fixer parfaitement sur l’antigène présenté. Un peu comme un serrurier qui copierait des centaines de clés les unes à la suite des autres, jusqu’à ce que l’une d’entre elles, légèrement différente, entre enfin dans la serrure. Ces clés, ce sont les anticorps. Certains filent dans le sang : les IgG ou les IgM. Mais d’autres vont préférentiellement dans les muqueuses : les IgA.

    Ces IgA apparaissent de plus en plus comme les héros de l’ombre de cette histoire. De fait, on les trouve peu, ou de manière très transitoire, dans le sang. Depuis notre trou de serrure, ils sont donc quasi invisibles. « L’industrie fabrique toute la logistique en masse pour le sang (tubes, aiguilles, etc.) », explique Guy Gorochov, responsable du Centre d’immunologie et des maladies infectieuses de l’université Pierre-et-Marie-Curie. « La salive, qui est un bon reflet des sécrétions mucosales, n’est pas encore un liquide biologique de grande routine. C’est culturel, mais cela devrait rapidement évoluer, étant donné la situation actuelle », indique ce chercheur parisien. En outre, la salive est un milieu plein de germes en tous genres, donc plus délicat à évaluer d’un point de vue immunologique.

    Pourtant, pour peu que l’on accepte d’aller fouiner dans les sécrétions buccales, nasales, bronchiques ou même lacrymales, on découvre d’importantes quantités d’IgA chez les personnes infectées. Guy Gorochov et son équipe mènent actuellement une étude sur 145 patients Covid (prépublication en cours de relecture https://www.medrxiv.org/content/10.1101/2020.06.10.20126532v1 ). « Dans les premières semaines suivant l’apparition des symptômes, la neutralisation du SRAS-CoV-2 repose vraisemblablement davantage sur les IgA que sur les IgM ou les IgG, résume l’immunologiste. Les IgA apparaissent en effet en premier et s’avèrent beaucoup plus puissants que les IgG et les IgM pour neutraliser le virus in vitro. Par ailleurs, on en détecte encore trois mois après les premiers symptômes dans la salive… »

    Une autre étude menée en Suisse https://www.biorxiv.org/content/10.1101/2020.05.21.108308v1 révèle que plus les patients sont jeunes, plus ils sont susceptibles d’avoir des taux d’IgA importants dans leurs sécrétions nasales. Mais plus étonnant encore : certains patients possèdent des taux élevés d’IgA dans leur nez, alors même qu’aucun autre anticorps (ni IgG ni IgM) ne circule dans leur sang.

    Ces découvertes interrogent : cette réaction immunitaire locale pourrait-elle être suffisante pour faire obstacle à la maladie et mettre en échec les infections ultérieures ? « C’est bien joli de neutraliser le virus in vitro, mais est-ce que ces IgA nous protègent dans la vraie vie ? Seules des études à plus grande échelle permettraient de le savoir », tempère Guy Gorochov. Si tel était le cas, nous serions alors plus nombreux à être immunisés que ce que les mesures sanguines veulent bien refléter. Ce qui serait une excellente nouvelle…

    Et les IgA ne sont pas les seuls héros invisibles depuis notre trou de serrure. Les mesures classiques de notre immunité passent également à côté d’un autre acteur, qui apparaît de plus en plus majeur dans notre réponse au SARS-CoV-2 : le lymphocyte T, également appelé cellule T.

    Contrairement à leurs cousins les lymphocytes B, les lymphocytes T ne fabriquent pas d’anticorps en série. Pour reprendre l’analogie du serrurier, eux conservent leur clé magique autour du cou et se baladent ensuite dans la lymphe et le sang. Par ailleurs, cette clé ne leur permet pas de repérer un pathogène qui circule librement dans notre corps, comme le font les anticorps. Elle leur permet en revanche de détecter les cellules en train d’être infectées par un virus. Dans ce cas, les lymphocytes T sortent l’artillerie lourde : ils détruisent les virus mais aussi les cellules infectées. On appelle cela l’immunité cellulaire.

    Et ce n’est pas tout : ces cellules T peuvent également stimuler les lymphocytes B à déverser leurs anticorps et aussi activer directement les cellules phagocytaires, pour relancer la première étape de défense au niveau du ou des sites d’infection. Pour les scientifiques, les lymphocytes T sont les véritables chefs d’orchestre de notre système immunitaire.

    Les études qui se sont penchées sur ces cellules en trouvent quasi systématiquement dans le sang des personnes qui ont été contaminées par le SARS-CoV-2 (voir notamment les travaux menés à Strasbourg https://www.medrxiv.org/content/10.1101/2020.06.21.20132449v1.full.pdf , en Suède https://www.biorxiv.org/content/10.1101/2020.06.29.174888v1.full.pdf , à Berlin https://www.medrxiv.org/content/10.1101/2020.04.17.20061440v1.full.pdf ou en Californie https://pubmed.ncbi.nlm.nih.gov/32473127 ). Tout comme les IgA, on en détecte également chez des personnes exposées au virus mais n’ayant jamais développé de symptômes et dont la sérologie classique ne révèle aucun anticorps circulant. Dans l’étude suédoise, parmi 30 personnes proches de cas diagnostiqués et 55 donneurs de sang, les deux tiers présentaient des lymphocytes T dans leur sang mais pas d’anticorps IgG anti SARS-CoV-2.

    Plus frappant encore : on retrouve des lymphocytes T qui réagissent au SARS-CoV-2 dans des échantillons de sang prélevés… avant 2019, donc avant la pandémie ! Dans l’étude menée en Californie, de tels lymphocytes étaient ainsi détectés dans la moitié des 20 échantillons de sang prélevés entre 2015 et 2018. « Cela pourrait refléter l’existence, chez certains individus, d’une immunité croisée préexistante », concluent les auteurs. Autrement dit, des personnes ayant été en contact avec d’autres coronavirus dans le passé auraient pu fabriquer des lymphocytes T capables de reconnaître non seulement l’espèce précise de coronavirus à laquelle ils avaient été confrontés, mais aussi d’autres espèces voisines, dont le SARS-CoV-2. Un peu comme s’ils étaient dotés d’une clé passe-partout capable d’ouvrir différentes serrures relativement proches.

    D’ailleurs, en analysant de plus près ces lymphocytes, les chercheurs se rendent compte qu’ils réagissent avec la protéine Spike, ancrée dans l’enveloppe du virus et qui lui permet de pénétrer à l’intérieur des cellules (la protéine cible des vaccins en développement). Mais pas seulement. Une étude, publiée dans Nature https://www.nature.com/articles/s41586-020-2550-z , s’est penchée sur le cas de 23 survivants au SARS-CoV-1, le coronavirus qui avait sévi en 2003 (plus souvent appelé SRAS en français). Tous possèdent des lymphocytes T qui réagissent à une autre protéine appelée N, associée à l’ARN du virus et contenue à l’intérieur de l’enveloppe.

    Problème : mesurer et analyser ces lymphocytes T nécessite des techniques d’analyse beaucoup plus lourdes et coûteuses que pour les anticorps. Impossible pour l’heure de les tester en routine. « En se basant sur les tests sérologiques, on sous-estime ainsi clairement la proportion de la population exposée, en contact avec ce virus, affirme Fafi-Kremer, responsable du laboratoire de virologie du CHU de Strasbourg qui étudie la réponse lymphocytaire au virus. On sous-estime probablement aussi la part de la population immunisée contre ce virus. »

    « Probablement », car en réalité, « personne n’a pu démontrer la pertinence clinique de ces résultats », prévient Jean-Daniel Lelièvre, directeur du service d’immunologie clinique et maladies infectieuses de l’hôpital Henri-Mondor. « Il est possible, comme dans le cas du sida, que ces lymphocytes T ne nous protègent pas d’une infection ultérieure. En revanche, ils pourraient nous éviter de faire une maladie grave. C’est ce que les études sont en train de rechercher », annonce ce spécialiste, qui analyse actuellement toutes les publications d’immunologie sur le Covid pour le compte de la Haute Autorité de santé.

    « Intuitivement, on peut penser que [les lymphocytes T] nous protègent mais l’immunologie est l’endroit où l’intuition se meurt », dit Donna Farber https://www.theatlantic.com/health/archive/2020/08/covid-19-immunity-is-the-pandemics-central-mystery/614956 , microbiologiste à l’université Columbia (New York). Là est sans doute la grande leçon de toutes ces publications qui s’amoncellent sur notre réponse immunitaire : nous en savons si peu qu’il est bien difficile d’en tirer de quelconques enseignements pratiques.

    « On ne dispose pas du périscope pour suivre les agissements du système immunitaire », rappelle Anne-Marie Moulin, médecin et historienne des sciences. Nos tests sérologiques nous donnent une vision tronquée de la réalité. Voilà qui pourrait expliquer les faibles taux de séropositivité dans des régions pourtant fortement touchées par la pandémie. Et pourquoi, malgré ce faible taux de séropositivité, on n’observe (encore) que très peu de cas de réinfection.

    Cependant, cette vision tronquée pourrait nous fourvoyer dans le développement des vaccins. Bon nombre de projets se concentrent uniquement sur les anticorps circulants capables de neutraliser une seule protéine du virus : la fameuse Spike. « Il est important de ne pas se concentrer sur une seule protéine », préviennent certains spécialistes https://www.sciencemag.org/news/2020/05/t-cells-found-covid-19-patients-bode-well-long-term-immunity . « Il faudrait aussi songer à déclencher une réponse IgA au niveau des muqueuses », suggère Guy Gorochov. Pour cela, l’une des solutions serait de tester des vaccins par voie nasale. Mais pour l’heure, tous les vaccins en phase 3 passent par des injections intramusculaires, peu susceptibles de réveiller nos IgA…

    Accordons à ce virus au moins un mérite : celui de nous forcer à prendre place sur les gradins de notre théâtre immunitaire. Vu d’ici, le spectacle met à l’honneur des zones de notre corps trop souvent négligées, comme notre muqueuse nasale, ainsi que d’autres acteurs de notre système immunitaire au-delà des habituels anticorps circulants. La pandémie a révélé l’importance d’une réponse localisée et différenciée en fonction des caractéristiques des zones touchées. De même, il semble désormais nécessaire d’adopter un regard beaucoup plus territorialisé et diversifié de notre corps pour appréhender son immunité.

    #covid19 #SARS-CoV-2 #immunologie #immunité

  • Why Aren’t We Talking More About Ventilation ? - The Atlantic

    How is it that six months into a respiratory pandemic, we are still doing so little to mitigate airborne transmission?
    Zeynep Tufekci
    July 30, 2020

    The coronavirus reproduces in our upper and lower respiratory tracts, and is emitted when we breathe, talk, sing, cough, or sneeze. Figuring out how a pathogen can travel, and how far, under what conditions, and infect others—transmission—is no small deal, because that information enables us to figure out how to effectively combat the virus. For COVID-19, perhaps the most important dispute centers specifically on what proportion of what size droplets are emitted from infected people, and how infectious those droplets are, and how they travel. That the debate over the virus’s modes of transmission is far from over is not a surprise. It’s a novel pathogen. The Columbia University virologist Angela Rasmussen told me that, historically, it took centuries to understand how pathogens such as the plague, smallpox, and yellow fever were transmitted and how they worked. Even with modern science, there are still debates about how influenza, a common annual foe, is transmitted.

    There is a big dispute in the scientific community, however, about both the size and the behavior of these particles, and the resolution of that question would change many recommendations about staying safe. Many scientists believe that the virus is emitted from our mouths also in much smaller particles, which are infectious but also tiny enough that they can remain suspended in the air, float around, be pushed by air currents, and accumulate in enclosed spaces—because of their small size, they are not as subject to gravity’s downward pull. Don Milton, a medical doctor and an environmental-health professor at the University of Maryland, compares larger droplets “to the spray from a Windex dispenser” and the smaller, airborne particles (aerosols) “to the mist from an ultrasonic humidifier.” Clearly, it’s enough to merely step back—distance—to avoid the former, but distancing alone would not be enough to avoid breathing in the latter.

    In multiple studies, researchers have found that COVID-19’s secondary attack rate, the proportion of susceptible people that one sick person will infect in a circumscribed setting, such as a household or dormitory, can be as low as 10 to 20 percent. In fact, many experts I spoke with remarked that COVID-19 was less contagious than many other pathogens, except when it seemed to occasionally go wild in super-spreader events, infecting large numbers of people at once, across distances much greater than the droplet range of three to six feet. Those who argue that COVID-19 can spread through aerosol routes point to the prevalence and conditions of these super-spreader events as one of the most important pieces of evidence for airborne transmission.

    All this has many practical consequences. As Marr, from Virginia Tech, says, if aerosols are crucial, we should focus as much on ventilation as we do on distancing, masks, and hand-washing, which every expert agrees are important. As the virologist Ryan McNamara of the University of North Carolina told me, all these protections stack on top of one another: The more tools we have to deploy against COVID-19, the better off we are. But, it’s still important for the public to have the correct mental model of the reasoning behind all the mitigations, since even those agreed-upon protections don’t all behave the same way under an aerosol regime.

    As another example, you may have seen the many televised indoor events where the audience members are sitting politely distanced and masked, listening to the speaker, who is the only unmasked person in the room. Jimenez, the aerosol expert, pointed out to me that this is completely backwards, because the person who needs to be masked the most is the speaker, not the listeners. If a single mask were available in the room, we’d put it on the speaker. This is especially important because cloth masks, while excellent at blocking droplets (especially before they evaporate and become smaller, thus more likely to be able to float), aren’t as effective at keeping tinier aerosol particles out of the wearer’s mouth and nose once they are floating around the room (though they do seem to help). We want to see the speaker’s mouth, one might say, but that is a problem we can approach creatively—face shields that wrap around the head and seal around the neck, masks with transparent portions that can still filter, etc.—once we stop ignoring the problem. In fact, designing a high-filtration but transparent mask or face shield might be an important solution in classrooms as well, to help keep teachers safe.

    Once we pay attention to airflow, many other risks look different. Dylan Morris, a doctoral candidate at Princeton and a co-author of the first paper to confirm that the virus could remain infectious in aerosolized form, under experimental conditions, showed me a clip of a group of people in a conga line, separated six feet apart by ropes. They were merrily dancing, everyone standing behind someone else, in their slipstream—exactly where you don’t want to be, inhaling aerosol clouds from panting people. Similarly, Jimenez pointed out that, when a masked person is speaking, the least safe location might be beside them or behind them, where the aerosols can escape from the mask, though ordinarily, under a droplet regime, we would consider the risk to only be in front of them. The importance of aerosols may even help explain why the disease is now exploding in the southern United States, where people often go into air-conditioned spaces to avoid the sweltering heat.

    There are two key mitigation strategies for countering poor ventilation and virus-laden aerosols indoors: We can dilute viral particles’ presence by exchanging air in the room with air from outside (and thus lowering the dose, which matters for the possibility and the severity of infection) or we can remove viral particles from the air with filters.

    Consider schools, perhaps the most fraught topic for millions. Classrooms are places of a lot of talking; children are not going to be perfect at social distancing; and the more people in a room, the more opportunities for aerosols to accumulate if the ventilation is poor. Most of these ventilation issues are addressable, sometimes by free or inexpensive methods, and sometimes by costly investments in infrastructure that should be a national priority.

    #Zeynep_Tufekci #Aerosol #Ventilation #COVID-19

  • Why Aren’t We Talking More About #Ventilation? - The Atlantic

    Strikingly, in one database of more than 1,200 super-spreader events, just one incident is classified as outdoor transmission, where a single person was infected outdoors by their jogging partner, and only 39 are classified as outdoor/indoor events, which doesn’t mean that being outdoors played a role, but it couldn’t be ruled out. The rest were all indoor events, and many involved dozens or hundreds of people at once. Other research points to the same result: Super-spreader events occur overwhelmingly in indoor environments where there are a lot of people.

    #covid-19 #transmission

  • The Pandemic Experts Are Not Okay - by Ed Yong (The Atlantic)

    But Gonsalves added that HIV veterans have a deep well of emotional reserves to draw from, and a sense of shared purpose to mobilize. His advice to the younger generation is twofold. First, don’t ignore your feelings: “Your anxiety, fear, and anger are all real,” he said. Then, find your people. “They may not be your colleagues,” he said, and they might not be scientists. But they’ll share the same values, and be united in recognizing that “public health is not a career, but a mission and a calling.”

    #santé_publique et #santé_mentale

  • Jeudi 11 juin, Zeynep Tufekci invitée des Matins de France Culture

    Zeynep Tufekci, l’autrice de « Twitter & les gaz lacrymogènes » sera ce jeudi 11 juin l’invitée exceptionnelle des Matins de France Culture. Elle sera interviewée par Guillaume Erner de 7h45 à 8h45.

    L’occasion, en direct ou en podcast, de mieux connaître cette « technosociologue » dont nous avons publié la traduction française (par Anne Lemoine, qui a fait un excellent travail).

    Twitter & les gaz lacrymogènes
    Forces et fragilités de la contestation connectée
    Zeynep Tufekci
    ISBN 978-2-915825-95-4 - 430 p. - 29 €

    Zeynep Tufekci est de plus en plus remarquée aux États-Unis et partout dans le monde pour les suites qu’elle a donné à son livre, en particulier dans des éditoriaux dans The Atlantic ou The New York Times. Elle a été, dès le mois de janvier, une des premières à promouvoir la « distanciation sociale » et le port du masque, quand son pays ne croyais pas au virus. Elle revenait de Hong Kong et avait pu comprendre la situation. De même, elle est en pointe sur les questions des médias sociaux et de l’élection de Trump (notamment le débat actuel entre Twitter et Facebook). Elle est enfin partie prenante des mobilisations anti-racistes qui secouent les États-Unis (et qui s’étendent, notamment chez nous). Le bon moment pour une interview.

    Je vous mets ci-après pour celles et ceux qui lisent l’anglais une liste de référence de ses articles récents sur ces sujets.

    Nous avons également produit un petit livre numérique autour de Zeynep Tufekci, intitulé « Le monde révolté ». Celui-ci comporte la traduction d’un texte autobiographique de Zeynep et un long article de Gus Massiah. Il est gratuit (complètement, on ne demande même pas de mail ou autre, cadeau on vous dit). Vous pouvez l’obtenir à :

    Bonne écoute et bonne lecture,

    Hervé Le Crosnier

    Voici quelques références récentes sur les publications de Zeynep Tufekci en anglais pour celles et ceux qui lisent la langue de Shakespeare.

    Preparing for Coronavirus to Strike the U.S. - Scientific American Blog Network

    Opinion | Why Telling People They Don’t Need Masks Backfired - The New York Times

    What Really Doomed America’s Coronavirus Response - The Atlantic

    Closing the Parks Is Ineffective Pandemic Theater - The Atlantic

    Don’t Wear a Mask for Yourself - The Atlantic

    Trump’s Executive Order Isn’t About Twitter - The Atlantic

    The Case for Social Media Mobs - The Atlantic

    How a Bad App—Not the Russians—Plunged Iowa Into Chaos - The Atlantic

    Hong Kong Protests : Inside the Chaos - The Atlantic

    #Zeynep_Tufekci #France_Culture

  • The Pandemic Doesn’t Have to Be This Confusing - The Atlantic

    Past coronavirus epidemics offer limited clues because they were so contained: Worldwide, only 10,600 or so people were ever diagnosed with SARS or MERS combined, which is less than the number of COVID-19 cases from Staten Island. “For new diseases, we don’t see 100 to 200 patients a week; it usually takes a whole career,” says Megan Coffee, an infectious-disease doctor at NYU Langone Health. And “if you see enough cases of other diseases, you’ll see unusual things.” During the flu pandemic of 2009, for example, doctors also documented heart, kidney, and neurological problems. “Is #COVID-19 fundamentally different to other diseases, or is it just that you have a lot of cases at once?” asks Vinay Prasad, a hematologist and an oncologist at Oregon Health and Science University.

    Prasad’s concern is that COVID-19 has developed a clinical mystique—a perception that it is so unusual, it demands radically new approaches. “Human beings are notorious for our desire to see patterns,” he says. “Put that in a situation of fear, uncertainty, and hype, and it’s not surprising that there’s almost a folk medicine emerging.” Already, there are intense debates about giving patients blood thinners because so many seem to experience blood clots, or whether ventilators might do more harm than good. These issues may be important, and when facing new diseases, doctors must be responsive and creative. But they must also be rigorous. “Clinicians are under tremendous stress, which affects our ability to process information,” McLaren says. “‘Is this actually working, or does it seem to be working because I want it to work and I feel powerless?’”

  • Don’t Wear a Mask for Yourself - The Atlantic

    If you feel confused about whether people should wear masks and why and what kind, you’re not alone. COVID-19 is a novel disease and we’re learning new things about it every day. However, much of the confusion around masks stems from the conflation of two very different functions of masks.

    Masks can be worn to protect the wearer from getting infected or masks can be worn to protect others from being infected by the wearer. Protecting the wearer is difficult: It requires medical-grade respirator masks, a proper fit, and careful putting on and taking off. But masks can also be worn to prevent transmission to others, and this is their most important use for society. If we lower the likelihood of one person’s infecting another, the impact is exponential, so even a small reduction in those odds results in a huge decrease in deaths. Luckily, blocking transmission outward at the source is much easier. It can be accomplished with something as simple as a cloth mask.

    The good news is that preventing transmission to others through egress is relatively easy. It’s like stopping gushing water from a hose right at the source, by turning off the faucet, compared with the difficulty of trying to catch all the drops of water after we’ve pointed the hose up and they’ve flown everywhere. Research shows that even a cotton mask dramatically reduces the number of virus particles emitted from our mouths—by as much as 99 percent. This reduction provides two huge benefits. Fewer virus particles mean that people have a better chance of avoiding infection, and if they are infected, the lower viral-exposure load may give them a better chance of contracting only a mild illness.

    COVID-19 has been hard to control partly because people can infect others before they themselves display any symptoms—and even if they never develop any illness. Three recent studies show that nearly half of patients are infected by people who aren’t coughing or sneezing yet. Many people have no awareness of the risk they pose to others, because they don’t feel sick themselves, and many may never become overtly ill.

    Models show that if 80 percent of people wear masks that are 60 percent effective, easily achievable with cloth, we can get to an effective R0 of less than one. That’s enough to halt the spread of the disease. Many countries already have more than 80 percent of their population wearing masks in public, including Hong Kong, where most stores deny entry to unmasked customers, and the more than 30 countries that legally require masks in public spaces, such as Israel, Singapore, and the Czech Republic. Mask use in combination with physical distancing is even more powerful.

    We know a vaccine may take years, and in the meantime, we will need to find ways to make our societies function as safely as possible. Our governments can and should do much—make tests widely available, fund research, ensure medical workers have everything they need. But ordinary people are not helpless; in fact, we have more power than we realize. Along with keeping our distance whenever possible and maintaining good hygiene, all of us wearing just a cloth mask could help stop this pandemic in its tracks.

    #COVID-19 #Masques #Zeynep_Tufekci

  • Zeynep Tufekci - Why the World Health Organization Failed - The Atlantic

    Trump’s ploy to defund the WHO is a transparent effort to distract from his administration’s failure to prepare for the COVID-19 pandemic. It would be disastrous too. Many nations, especially poor ones, currently depend on the WHO for medical help and supplies. But it is also true that in the run-up to this pandemic, the WHO failed the world in many ways. However, President Trump’s move is precisely the kind of political bullying that contributed to the WHO’s missteps.

    The WHO failed because it is not designed to be independent. Instead, it’s subject to the whims of the nations that fund it and choose its leader. In July 2017, China moved aggressively to elect its current leadership. Instead of fixing any of the problems with the way the WHO operates, Trump seems to merely want the United States to be the bigger bully.

    This mission-driven WHO would not have brazenly tweeted, as late as January 14, that “preliminary investigations conducted by the Chinese authorities have found no clear evidence of human-to-human transmission of the novel #coronavirus (2019-nCoV) identified in #Wuhan, #China.” That claim was false, and known by the authorities in Wuhan to be false.. Taiwan had already told the WHO of the truth too. On top of that, the day before that tweet was sent, there had been a case in Thailand: a woman from Wuhan who had traveled to Thailand, but who had never been to the seafood market associated with the outbreak—which strongly suggested that the virus was already spreading within Wuhan.

    We can get a glimpse at that alternate timeline by looking at the two places where COVID-19 was successfully contained: Taiwan and Hong Kong. With dense populations and close links to and travel from China, Taiwan and Hong Kong are unlikely candidates for success. Yet Taiwan reported zero new confirmed cases on Tuesday, fewer than 400 confirmed cases since the beginning of the outbreak, and only six deaths. Taiwan’s schools have been open since the end of February and there is no drastic lockdown in the island of almost 30 million people.

    Taiwan and Hong Kong succeeded because they ignored, contradicted, and defied the official position and the advice of the WHO on many significant issues. This is not a coincidence, but a damning indictment of the WHO’s leadership.

    Taiwan’s and Hong Kong’s health authorities assessed the pandemic accurately, and not just with respect to the science. They understood the political complexities, including the roles of the WHO and China in shaping official statements about the virus. They did not take the WHO’s word when it was still parroting in late January China’s cover-up that there was no human-to-human transmission. They did not listen to the WHO on not wearing masks, which the WHO continues to insist are unnecessary to this late day, despite accumulating evidence that masks are essential to dampening this epidemic’s spread. Taiwan ignored the WHO’s position that travel bans were ineffective; instead, it closed its borders early and, like Hong Kong, screened travelers aggressively.

    Hong Kong and Taiwan remembered that China has a history of covering up epidemics.

    When independent access to Wuhan was denied, instead of simply relaying what China claimed as if it were factual, the WHO could have notified the world that an alarming situation was unfolding. It could have said that China was not allowing independent investigations, and that there were suggestions of human-to-human transmission that needed urgent investigation. That would have gotten the world’s attention. And it could have happened the first week of January, mere days after China reported 41 cases of a mysterious pneumonia, but before China’s first announced COVID death. This is when Taiwan banned travel from Wuhan and started aggressive screening of travelers who had been there in recent weeks. It’s also when Taiwan ramped up its domestic mask production, in order to distribute masks to its whole population, despite WHO (still!) claiming they aren’t necessary.

    Many countries may not have had their first imported case until late January or early February. Researchers estimate that acting even a week or two early might have reduced cases by 50 to 80 percent. With proper global leadership, we may have had a very different trajectory.

    A mission-driven WHO would not have repeatedly praised China for its “transparency,” (when it was anything but) nor would it have explicitly criticized travel bans when they were being imposed on China but remained silent when China imposed them on other nations. Strikingly, the only country the WHO’s leader, Tedros Adhanom Ghebreyesus, has directly criticized is Taiwan, whose diplomats he accused (without proof) of being involved in racist attacks on him. Unfortunately, the WHO seems to remember its principles only when they align with China’s interests.

    Be that as it may, President Trump’s own attempt to bully the WHO is worse than being merely a distraction from his own lack of preparation and the spectacular public-health failure that is now unfolding across the United States. The president wants to break the WHO even more dramatically, in precisely the way it is already broken. He wants it to bow to the outsize influence of big powerful nations at the expense of its mission.

    Defunding the WHO is not just foolish. It is dangerous: A pandemic needs to be contained globally, including in the poor countries that depend on the WHO. The WHO is the only global organization whose mission, reach, and infrastructure are suitable for this. The U.S. funds about 15 percent of the WHO’s current budget, and the already stretched-thin organization may not be able to quickly make that up.

    We must save the WHO, but not by reflexively pretending that nothing’s wrong with it, just because President Trump is going after the organization. We should be realistic and honest about the corruption and shortcomings that have engulfed the leadership of an organization that is deeply flawed, but that is still the jewel of the international health community.

    #OMS #Chine #Etats-Unis #Santé_publique

  • Closing the Parks Is Ineffective Pandemic Theater - The Atlantic

    Par Zeynep Tufekci

    In the short run, closing parks may seem prudent, when our hospitals are overrun and we are trying so hard to curb the spread of COVID-19. But in the medium to long run, it will turn out to be a mistake that backfires at every level. While it’s imperative that people comply with social-distancing and other guidelines to fight this pandemic, shutting down all parks and trails is unsustainable, counterproductive, and even harmful.

    To start with, the park crackdown has an authoritarian vibe. In closing Brockwell Park, for example, pictures showed two police officers approaching a lone sunbather, who was nowhere near anyone else—well, except the police, who probably had something better to do. Such heavy-handedness might even make things worse, as it may well shift the voluntary compliance we see today into resistance.

    Finding sustainable policies is crucial, especially since this pandemic likely isn’t going away in a few weeks. It’s plausible that we will be social distancing, on and off, for another year. That means we need to consider how to maintain compliance with strict measures over that long of a time.

    he outdoors, exercise, sunshine, and fresh air are all good for people’s immune systems and health, and not so great for viruses. There is a compelling link between exercise and a strong immune system. A lack of vitamin D, which our bodies synthesize when our skin is exposed to the sun, has long been associated with increased susceptibility to respiratory diseases. The outdoors and sunshine are such strong factors in fighting viral infections that a 2009 study of the extraordinary success of outdoor hospitals during the 1918 influenza epidemic suggested that during the next pandemic (I guess this one!) we should encourage “the public to spend as much time outdoors as possible,” as a public-health measure.

    Read: How the 1918 pandemic frayed social bonds

    Mental health is also a crucial part of the resilience we need to fight this pandemic. Keeping people’s spirits up in the long haul will be important, and exercise and the outdoors are among the strongest antidepressants and mental-health boosters we know of, often equaling or surpassing drugs and/or therapy in clinical trials. Stress has long been known to be a significant suppressor of immunity, and not being able to get some fresh air and enjoy a small change of scenery will surely add to people’s stress. We may well be facing a spike in suicides and violence as individuals and families face significant stress and isolation: The Air Force Academy initially imposed drastic isolation on its cadets due to the coronavirus, but had to reverse course after two tragic suicides. Domestic violence is another real concern: Not having a place to go, even for an hour, may greatly worsen conditions in some households.

    The history of disaster response is full of examples of extraordinary goodwill and compliance among ordinary people that disintegrate after authorities come down with heavy-handed measures that treat the public as an enemy. Rebecca Solnit’s book A Paradise Built in Hell details many such cases, such as the lives lost when the military was ordered into post-earthquake San Francisco in 1906 to control the dangerous and unruly “unlicked mob” that was primarily a figment of the authorities’ imagination. Unfortunately, the official response worsened the subsequent fire (which was more damaging than the earthquake itself) by keeping away volunteers “who might have supplied the power to fight the fire by hand.” Some ordinary citizens were even shot by soldiers on the lookout for these alleged mobs of looters and dangerous behavior from citizens. Similarly, in the aftermath of Hurricane Katrina, as a review of Solnit’s book summarized, “there were myriad accounts of paramedics being kept from delivering necessary medical care in various parts of the city because of false reports of violence.”

    When the efforts to “flatten the curve” start working and the number of known infections starts going down, authorities will need to be taken seriously. Things will look better but be far, far from over. If completely kept indoors with no outlet for a long time, the public may be tempted to start fully ignoring the distancing rules at the first sign of lower infection rates, like an extreme dieter who binges at a lavish open buffet. Just like healthy diets, the best pandemic interventions are sustainable, logical, and scientifically justified. If pandemic theater gets mixed up with scientifically sound practices, we will not be able to persuade people to continue with the latter.

    This doesn’t mean we shouldn’t limit park attendance at all, but there are better answers than poorly planned full closures.

    Governments could make a special appeal to people who have yards to leave parks for those who do not. (Wealthier people tend to have their own yards or lots, which is another reason not to shut down parks and deny outdoor access to poorer people.)

    #Zeynep_Tufekci #Espaces_verts #Coronavirus #Exercice #Autoritarisme

  • How Will the Coronavirus End? - Ed Yong (The Atlantic)

    The U.S. may end up with the worst COVID-19 outbreak in the industrialized world. This is how it’s going to play out.

    #prospective (trop déprimé pour lire en détail ; l’article conclut en croyant toujours à l’exception américaine)

    The Crisis Could Last 18 Months. Be Prepared., by Juliette Kayyem, Former Department of Homeland Security official - The Atlantic

    The shutdowns happened remarkably quickly, but the process of resuming our lives will be far more muddled.

  • Forum ouvert par le Network for Computational Modeling in Social and Ecological Sciences (#CoMSES) pour que la communauté ABM puisse échanger sur le sujet :


    –-> Vous pourrez notamment y trouver une revue/veille des démarches de modélisation de l’épidémie.

    #modélisation #covid-19 #coronavirus #épidémie


    PS. Je mets ci-dessous dans ce fil de discussion des liens vers des sites qui proposent des modélisations que je reçois notamment via la mailing-list geotamtam... mais... je n’y connais rien... donc aucune idée de ce que partage (ceci dit, ça vient d’un réseau de chercheurs...), je me dis que ça peut peut-être servir à quelques seenthisien·nes...

  • Why Do People Still Love Consumer Tech ? - The Atlantic

    Everywhere I turned, there were signs that I didn’t totally understand. “Can textiles empower mothers to share their personal experience of pregnancy ?” one big, blue banner asked, fighting for attention among hundreds of others in a cavernous exhibition hall. “Shop with your DNA,” implored another. Just around the corner, in lofted lights, a company promised that its products are “where sleep tech meets holistic wellness.” Across the room, a plumbing-fixture company got right down to business (...)

    #domotique #technologisme #domination #InternetOfThings #marketing

  • The Rise of Identity Fusion and Allegiance to Trump - The Atlantic

    The idea was never fully formed, and Lecky died at just 48, his work unpublished. But today, the basic concept is seeing a renewed interest from scholars who think Lecky was truly onto something. When the psychologist’s students compiled his writing posthumously, in 1945, the postwar world was grappling with how humans were capable of such catastrophic cruelty. Surely entire armies had not been motivated by their relationships with their mothers. The early science of the mind was beginning to delve into the timeless questions of philosophy and religion: Why do we do destructive things—to others, and to ourselves? Why do we so often act against our own interests? Why would a young boy risk his acceptance to Harvard to pile manure into a school gym?

    These questions meant studying the roots of identity, and how a person could be at peace with being hateful and even dangerous. Now, decades later, an emerging explanation points to something more insidious than the possibility that someone simply identifies with a malicious group or blindly follows a toxic person. Instead, out of a basic need for consistency, we might take on other identities as our own.

    The process of de-fusing, then, might involve offering alternative systems of creating consistency and order. If people who are inclined to fusion have the option to fuse with entities that do not wish to exploit them, and that are generally good or neutral for the world, they might be less likely to fuse with, say, a demagogue. “But, of course,” Dovidio says, “that’s hard.”

    #fusion #psychologie_sociale