New Playbook for Covid-19 Protection Emerges After Year of Study, Missteps

Scientists are settling on a road map that can help critical sectors of the economy safely conduct business, from meatpacking plants to financial services, despite the pandemic’s continued spread.

After nearly a year of study, the lessons include: Mask-wearing, worker pods and good air flow are much more important than surface cleaning, temperature checks and plexiglass barriers in places like offices and restaurants. And more public-health experts now advocate wide use of cheap, rapid tests to detect cases quickly, in part because many scientists now think more than 50% of infections are transmitted by people without symptoms.

The playbook comes after months of investigations on how the coronavirus spreads and affects the body. Scientists combined that with knowledge gained from years of experience managing occupational-health hazards in high-risk workplaces, such as factories and chemical plants, where tiny airborne pollutants can build up and cause harm. They say different types of workplaces—taking into account the types of interactions workers have—need slightly different protocols.

The safety measures have taken on new urgency in recent weeks as new infections, hospitalizations and deaths rise across the U.S. and Europe, and potentially more-transmissible variants of the virus spread around the globe. This phase of the pandemic is prompting a new wave of stay-at-home orders, closures and travel restrictions, important first steps to curbing contagion. Infection-prevention specialists say known strategies for stemming spread should continue to work against the new variants, but that increased adherence is even more important.

Vaccines are rolling out, but slowly, and access will be limited mostly to high-priority groups for some time.

“We have to still deal with ‘the right now.’ We’ve zeroed in on this set of controls that we know work,” said Joseph Allen, director of the Healthy Buildings Program at the Harvard T.H. Chan School of Public Health.

Over the past year, the lack of consistent and cohesive messaging among scientists and lawmakers has seeded confusion over what makes up risky behavior, what activities should be avoided and why. That is beginning to change as consensus builds and scientists better understand the virus.

In the U.S., scientists at first advised people against wearing masks, in part because of shortages, while the idea of stay-at-home orders received severe pushback from some lawmakers. Early in the pandemic, testing was limited to people with symptoms, also partly due to shortages. That advice has shifted, but a year later, sufficient testing remains a critical issue.

Countries such as New Zealand and others in Asia adhered to a combination of basic mitigation strategies from the start—particularly masking, large-scale testing and lockdowns that broke transmission chains. They have tended to fare better than those that didn’t.

In one of his first moves, President Biden signed executive orders to require masks be worn on federal property and at airports and other transportation hubs. The administration said it is focusing on increasing the availability of vaccines, and also stressed the importance of widely available testing, which still lags in low-income and minority communities.

The current scientific playbook follows from two of the biggest research insights since the start of the pandemic. First, individuals who aren’t showing symptoms can transmit the virus. Infectious-disease experts worry most about this silent spread and say it is the reason the pandemic has been so hard to contain. While visibly sick people can pass on the virus, data cited by the Centers for Disease Control and Prevention estimate that 40% to 45% of those infected never develop symptoms at all. With the new viral variants that can transmit more readily, the potential for silent spread is even higher, infectious-disease experts said.

Secondly, researchers now know that tiny airborne particles known as aerosols play a role in the spread of Covid-19. These can linger in the air and travel beyond 6 feet.

An early hallmark of the pandemic response focused on the risk of transmission through large respiratory droplets that typically travel a few feet and then fall to the ground. Businesses rushed to buy plexiglass barriers, creating shortages.

The barriers can be good at preventing larger virus-containing droplets from landing on and infecting healthy individuals. They may offer some protection in shielding workers who have brief face-to-face interactions with many people throughout the workday, such as cashiers and receptionists, some occupational-health experts said.

Yet in settings like offices, restaurants or gyms, the role of the barriers is murkier, because activities like talking loudly and breathing deeply create aerosols that can waft on air currents and get around shields.

Also, installing such barriers could affect airflow throughout the space, environmental-health experts said. It is possible they could limit proper ventilation, making things worse, they said.

“There seems to be an assumption that particles are going to get stopped by the barriers, which is simply not true,” said Lisa Brosseau, an industrial hygienist and research consultant for the University of Minnesota’s Center for Infectious Disease Research and Policy. Airborne particles ferrying the virus “really distribute all over the place.”

The emphasis on intense surface cleaning has diminished as scientists have come to understand that indirect transmission through contaminated surfaces doesn’t play as critical a role in the spread of Covid-19 as they thought in the early days of the pandemic. In September, the CDC published sanitation guidelines for offices, workplaces, homes and schools that said that, for most surfaces, normal, routine cleaning should suffice, and that frequently touched objects, such as light switches and doorknobs, should be cleaned and disinfected.

“Sanitation is important in general always,” said Deborah Roy, president of the American Society of Safety Professionals. “The idea is we went overboard at the beginning because of the amount of unknowns. Now, we’re in a situation where we have more information.”

Temperature checks have become less popular among some employers because scientists now know that not all Covid-19 patients get fevers. One large study published online in November in the New England Journal of Medicine showed only 13% of Covid-19 patients reported a fever during the course of their illness.

Scientists now understand that brief encounters with an infected person can lead to spread, according to an October case study—an advance from earlier, when the rule of thumb was to avoid close contact for 15 consecutive minutes or longer. The report urged people to consider not just time and proximity in defining close contact with a Covid case, but also ventilation, crowding and a person’s likelihood of generating aerosols. Following the report, the CDC changed its definition of close contact to a total of 15 minutes or more over a 24-hour period.

Fresh air and effective filters indoors are important because they can remove virus particles before they have time to infect.

Masks offer a similar benefit, by lowering the amount of particles that infected individuals emit. Some scientists say there could be a benefit to doubling up on masks, as a second layer may improve both filtration and fit, so long as the masks are worn correctly.

A study published in October found that in countries where mask wearing was the norm or where governments put in place mask mandates, coronavirus mortality rates grew much more slowly than in countries without such measures. This fall, the CDC said that masks also offer some personal protection by reducing a wearer’s exposure to infected particles.

The combination of airborne particles and personal interactions, even among people who don’t feel ill, can turn wedding receptionsplane rides and choir practices into superspreading, potentially deadly events.

“For Covid, those two factors—asymptomatic spread and aerosolization—is what made mask-wearing so essential,” said Megan Ranney, emergency physician and assistant dean at Brown University.

Lessons can be gleaned from an outbreak at a Canadian spin studio last fall. The operators of the SPINCO studio in Hamilton, Ontario, had many public-health measures in place, including limiting the number of bikes in each class and screening staff and attendees with a questionnaire about topics including symptoms and travel. Rooms were sanitized within 30 minutes of a completed class, and towels were laundered, according to a statement provided last fall by Elizabeth Richardson, medical officer of health for the city of Hamilton.

Masks were also required before and after workout classes, Dr. Richardson said.

In total, 54 people who attended workouts over a span of several classes became infected. Another 31 cases were tied to the outbreak after spin-class attendees who contracted the virus then passed it on. The spin studio temporarily shut down following the outbreak and later reopened. It is currently not offering classes due to local regulations that mandated the closure of all gyms and fitness centers amid rising Covid-19 cases in the area.

In a November statement following the outbreak, Michelle August, founder of SPINCO, said that the company has “always put safety first and [has] exceeded all recommended guidelines from public health throughout” the pandemic. She said SPINCO has also strengthened and heightened its Covid-19 mitigation measures. SPINCO’s website currently says face masks are mandated throughout workouts in the company’s Hamilton location.

It also says that SPINCO is installing air purifiers in all of its studios that filter air in the rooms every 17 to 21 minutes. Airborne transmission experts recommend that building managers pump in clean, fresh air between three to six times an hour and that they install filters that are proven to effectively trap and remove a substantial number of virus-carrying particles.

To film a stage play of “A Christmas Carol” in November, the Guthrie Theater in Minneapolis upgraded its air filters and increased the rate at which the ventilation system pumps in outside air, said Brooke Hajinian, the Guthrie’s general manager. Management staggered arrival times, and a compliance officer made sure everyone socially distanced, wore their masks properly and washed their hands.

The theater divided staff into pods depending on how close they must get to the lone actor on stage, who portrayed Charles Dickens and didn’t wear a mask while performing, according to Ms. Hajinian. Those working nearest the stage underwent testing three times a week and wore N95 masks at all times, she said, while cleaning and security crews, who didn’t interact with the stage crews, wore cloth masks and didn’t undergo testing.

Actor Nathaniel Fuller performed in ‘A Christmas Carol’ at the Guthrie Theater in Minneapolis, where staff underwent tests often and workers disinfected the space. PHOTOS: KAITLIN SCHLICK(3)

Ms. Hajinian said she monitored the staff’s testing results and symptoms. “Any symptom is not a failure of this plan,” she said. Catching a case “and isolating it—that’s what success looks like for us,” she said. There were no cases, she said.

Scientists say multilayered safety efforts are needed because no single prevention method is 100% effective.

One of the largest studies of asymptomatic transmission to date showed that frequent testing was essential in identifying infections among a group of nearly 2,000 Marine recruits required to socially distance and wear masks except while eating and sleeping.

The study looked at cases identified with lab-based tests that search out and amplify the genetic material of the virus, but those tests aren’t as easily scaled as so-called rapid antigen tests, which search for viral proteins.

Results from lab-based tests can sometimes take days, while results from rapid tests are usually available in less than an hour. As a result, some epidemiologists have been advocating for widespread use of antigen tests to prevent outbreaks, because they are cheaper and don’t require high-tech laboratory equipment to run, meaning they can be deployed in a broader range of settings.

The shift toward using frequent, inexpensive and rapid tests on the same people multiple times a week to screen entire populations—instead of one-time tests on individuals who have symptoms—will be important to efficiently break transmission chains, epidemiologists said.

“Unless we’re doing really broad, frequent screening of the people at large, we’re completely missing the vast majority” of infections, said Michael Mina, an assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health. “We have to change how we’re doing this.”

While rapid tests tend to be less sensitive than lab-based tests, Dr. Mina said the data suggest they have high sensitivity when people are most likely to be infectious.

Other infectious-disease experts have touted contact tracing to identify and bust clusters of infection. But they say the strategy works best when cases aren’t surging, as they are now. When transmission rates are too high, limiting gatherings, travel and crowding are more effective at denting spread, said Abraar Karan, a global-health physician at Brigham and Women’s Hospital and Harvard Medical School.

In places without big surges, a high-tech approach is becoming increasingly useful: genetic epidemiology, or tracking tiny changes in viral genomes to map out transmission chains. As the coronavirus replicates and moves from person to person, its genes change slightly. Sometimes, those tiny changes are unusual, and they can be particularly useful in mapping transmission events, according to Justin O’Grady, an infectious disease expert at the Quadram Institute in the U.K.

By sifting through the differences among more than 1,000 viral genomes, Dr. O’Grady and his collaborators found that a particular viral variant was moving through multiple nursing homes in the U.K., among patients and staff, but not among the wider community. The unpublished data suggested that transmission was facilitated by the movement of staff from one facility to another, Dr. O’Grady said. The team relayed the findings to government authorities and advised them to restrict staff moving among facilities during the pandemic.

“Sometimes genomic epidemiology is able to find hidden transmission links that traditional epidemiology would struggle to find,” Dr. O’Grady said. “We can’t stop transmission, but when we find a superspreader event…we can bring in the right prevention methods to stop it from spreading further.”

As Virus Grows Stealthier, Vaccine Makers Reconsider Battle Plans


As the coronavirus assumes contagious new forms around the world, two drug makers reported on Monday that their vaccines, while still effective, offer less protection against one variant and began revising plans to turn back an evolving pathogen that has killed more than two million people.

The news from Moderna and Pfizer-BioNTech underscored a realization by scientists that the virus is changing more quickly than once thought, and may well continue to develop in ways that help it elude the vaccines being deployed worldwide.

The announcements arrived even as President Biden banned travel to the United States from South Africa beginning on Saturday, in hopes of stanching the spread of one variant. And Merck, a leading drug company, on Monday abandoned two experimental coronavirus vaccines altogether, saying they did not produce a strong enough immune response against the original version of the virus.

Moderna and Pfizer-BioNTech both said their vaccines were effective against new variants of the coronavirus discovered in Britain and South Africa. But they are slightly less protective against the variant in South Africa, which may be more adept at dodging antibodies in the bloodstream.

The vaccines are the only ones authorized for emergency use in the United States.

As a precaution, Moderna has begun developing a new form of its vaccine that could be used as a booster shot against the variant in South Africa. “We’re doing it today to be ahead of the curve, should we need to,” Dr. Tal Zaks, Moderna’s chief medical officer, said in an interview. “I think of it as an insurance policy.”

“I don’t know if we need it, and I hope we don’t,” he added.

Moderna said it also planned to begin testing whether giving patients a third shot of its original vaccine as a booster could help fend off newly emerging forms of the virus.

Dr. Ugur Sahin, the chief executive of BioNTech, said in an interview on Monday that his company was talking to regulators around the world about what types of clinical trials and safety reviews would be required to authorize a new version of the Pfizer-BioNTech vaccine that would be better able to head off the variant in South Africa.

Studies showing decreased levels of antibodies against a new variant do not mean a vaccine is proportionately less effective, Dr. Sahin said.

BioNTech could develop a newly adjusted vaccine against the variants in about six weeks, he said. The Food and Drug Administration has not commented on what its policy will be for authorizing vaccines that have been updated to work better against new variants.

But some scientists said that the adjusted vaccines should not have to go through the same level of scrutiny, including extensive clinical trials, that the original versions did. The influenza vaccine is updated each year to account for new strains without an extensive approval process.

“The whole point of this is a rapid response to an emerging situation,” said John Moore, a virologist at Weill Cornell Medicine in New York.

Dr. Sahin said a similar booster shot eventually might be necessary to stop Covid-19. The vaccine’s reduced efficacy may also mean that more people would need to get the shots before the population achieves herd immunity.

Scientists had predicted that the coronavirus would evolve and might acquire new mutations that would thwart vaccines, but few researchers expected it to happen so soon. Part of the problem is the sheer ubiquity of the pathogen.CORONAVIRUS BRIEFING: An informed guide to the global outbreak, with the latest developments and expert advice.Sign Up

There have been nearly 100 million cases worldwide since the pandemic began, and each new infection gives the coronavirus more chances to mutate. Its uncontrolled spread has fueled the development of new forms that challenge human hosts in various ways.

“The more people infected, the more likely that we will see new variants,” said Dr. Michel Nussenzweig, an immunologist at Rockefeller University in New York. “If we give the virus a chance to do its worst, it will.”

Several variants have emerged with mutations that worry scientists. A form first detected in Britain is up to 50 percent more contagious than the virus identified in China a year ago, and researchers have begun to think that it may also be slightly more deadly.

Researchers in South Africa identified another variant after doctors there discovered a jump in Covid-19 cases in October. They alerted the World Health Organization in early December that the variant seemed to have mutations that might make the virus less susceptible to vaccines.Covid-19 Vaccines ›

While the exact order of vaccine recipients may vary by state, most will likely put medical workers and residents of long-term care facilities first. If you want to understand how this decision is getting made, this article will help.When can I return to normal life after being vaccinated?If I’ve been vaccinated, do I still need to wear a mask?Will it hurt? What are the side effects?Will mRNA vaccines change my genes?

A variant found in Brazil has many of the mutations seen in the South African form, but genetic evidence suggests that the two variants evolved independently. Preliminary studies in the laboratory had hinted that those viruses may have some degree of resistance to the immunity that people develop after recovering from the infection or being inoculated with the Moderna or Pfizer-BioNTech vaccines.

The variant identified in Britain has been found in at least 20 states in the United States. The version found in South Africa has not been reported in this country, but on Monday health officials in Minnesota announced that they had documented the first case of infection with the Brazilian variant.

It is far from certain that these are the only worrying variants out there. Few countries, including the United States, have invested in the kind of genetic surveillance needed to detect emerging variants. Britain leads the world in these efforts, sequencing of about 10 percent of its virus samples.

The United States has analyzed less than 1 percent of its samples; officials at the Centers for Disease Control and Prevention said this month that they expect to swiftly ramp up those efforts.

Researchers at Moderna examined blood samples from eight people who had received two doses of the vaccine, and two monkeys that had been immunized. Neutralizing antibodies — the type that can disable the virus — were just as effective against the variant identified in Britain as they were against the original form of the virus.

But with the variant circulating in South Africa, there was a sixfold reduction in the antibodies’ effectiveness. Even so, the company said, those antibodies “remain above levels that are expected to be protective.”

The results have not been published or peer-reviewed, but were posted online at BioRxiv. Moderna collaborated on the study with the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Dr. Zaks said that the new version of the Moderna vaccine, aimed at the South African variant, could be used if needed as a booster one year after people received the original vaccine.

The need for such a booster may be determined by blood tests to measure antibody levels or by watching the population of vaccinated people to see if they begin falling ill from the new variant.

“We don’t yet have data on the Brazilian variant,” Dr. Zaks said. “Our expectation is that if anything it should be close to the South African one. That’s the one with the most overlap.” New forms of the virus will continue to emerge, he said, “and we’ll continue to evaluate them.”

Noting that Moderna took 42 days to produce the original vaccine, he said the company could make a new one “hopefully a little faster this time, but not much.”

One reason the current vaccine remains effective is a “cushion effect,” meaning it provokes such a powerful immune response that it will remain highly protective even with some drop in antibody strength, Dr. Anthony S. Fauci, the government’s leading expert on infectious diseases, and President Biden’s adviser on the coronavirus, said at a news briefing on Friday.

Experts also cautioned against assuming that a decrease in neutralizing ability meant the vaccines were powerless against the new variants. Neutralizing antibodies are just one component of the body’s immune defense, noted Akiko Iwasaki, an immunologist at Yale University.

“In real life, there’s also T cells and memory B cells and non-neutralizing antibodies and all these other effectors that are going to be induced by the vaccine,” Dr. Iwasaki said. Neutralizing power is “very important, but it’s not the only thing that’s going to protect someone.”

So long as the authorized vaccines continue to work against the variants, the challenge will be to inoculate as many people as possible and to prevent the coronavirus from evolving into more impervious forms. “That for me is still the highest priority,” said Dr. Sahin, of BioNTech.

Then, he said, perhaps six to nine months later, people could be given a boost that was customized for the variant.

The pace of the vaccine rollout in the United States, at least, may be picking up. Dr. Fauci predicted on Sunday that two million inoculations daily might soon be possible.

But there are many countries where no one has been immunized. With richer countries buying up doses early, some populations may have to wait till 2022 at the earliest to gain access to any vaccines.

In theory, new variants emerging in other parts of the world could render the virus resistant to the vaccines, Dr. Nussenzweig said, and they would inevitably spread. It is therefore in everyone’s interest to immunize the world as quickly as possible, he added: “We can’t hermetically seal ourselves from the rest of the world.”

Hoping to contain the new variants, the administration has upheld bans on travel by noncitizens into the United States from Europe and Brazil. President Biden will ban travel by noncitizens from South Africa starting Saturday. But that variant may already be in the United States, researchers said.How Moderna’s Vaccine WorksTwo shots can prime the immune system to fight the coronavirus.

The mRNA technology used in both the Pfizer-BioNTech and Moderna vaccines allows them to be created and reformulated much faster than vaccines made with more traditional methods.

“This is the beauty of the mRNA vaccines — they’re very versatile,” Dr. Iwasaki said. But a new formulation may not even be necessary, she added. A third dose of the current vaccine may be enough to boost levels of antibodies.

Dr. Zaks said that discussions with regulators about what would be required to bring a new version of the vaccine to the public were just starting.

“It’s early days,” he said.

Could a Smell Test Screen People for Covid?


In a perfect world, the entrance to every office, restaurant and school would offer a coronavirus test — one with absolute accuracy, and able to instantly determine who was virus-free and safe to admit and who, positively infected, should be turned away.

That reality does not exist. But as the nation struggles to regain a semblance of normal life amid the uncontrolled spread of the virus, some scientists think that a quick test consisting of little more than a stinky strip of paper might at least get us close.

The test does not look for the virus itself, nor can it diagnose disease. Rather, it screens for one of Covid-19’s trademark signs: the loss of the sense of smell. Since last spring, many researchers have come to recognize the symptom, which is also known as anosmia, as one of the best indicators of an ongoing coronavirus infection, capable of identifying even people who don’t otherwise feel sick.

A smell test cannot flag people who contract the coronavirus and never develop any symptoms at all. But in a study that has not yet been published in a scientific journal, a mathematical model showed that sniff-based tests, if administered sufficiently widely and frequently, might detect enough cases to substantially drive transmission down.

Daniel Larremore, an epidemiologist at the University of Colorado, Boulder, and the study’s lead author, stressed that his team’s work was still purely theoretical. Although some smell tests are already in use in clinical and research settings, the products tend to be expensive and laborious to use and are not widely available. And in the context of the pandemic, there is not yet real-world data to support the effectiveness of smell tests as a frequent screen for the coronavirus. Given the many testing woes that have stymied pandemic control efforts so far, some experts have been doubtful that smell tests could be distributed widely enough, or made sufficiently cheat-proof, to reduce the spread of infection.

“I have been intimately involved in pushing to get loss of smell recognized as a symptom of Covid from the beginning,” said Dr. Claire Hopkins, an ear, nose and throat surgeon at Guy’s and St. Thomas’ Hospitals in the United Kingdom and an author of a recent commentary on the subject in The Lancet. “But I just don’t see any value as a screening test.”

A reliable smell test offers many potential benefits. It could catch far more cases than fever checks, which have largely flopped as screening tools for Covid-19. Studies have found that about 50 to 90 percent of people who test positive for the coronavirus experience some degree of measurable smell loss, a result of the virus wreaking havoc when it invades cells in the airway.

“It’s really like a function of the virus being in the nose at this exact moment,” said Danielle Reed, the associate director of the Monell Chemical Senses Center in Philadelphia. “It complements so much of the information you get from other tests.” Last month, Dr. Reed and her colleagues at Monell posted a study, which has not yet been published in a scientific journal, describing a rapid smell test that might be able to screen for Covid-19.

In contrast, only a minority of people with Covid-19 end up spiking a temperature. Fevers also tend to be fleeting, while anosmia can linger for many days.

A smell test could also come with an appealingly low price tag, perhaps as low as 50 cents per card, said Derek Toomre, a cell biologist at Yale University and an author on Dr. Larremore’s paper. Dr. Toomre hopes that his version will fit the bill. The test, the U-Smell-It test, is a small smorgasbord of scratch-and-sniff scents arrayed on paper cards. People taking the test pick away at wells of smells, inhale and punch their guess into a smartphone app, shooting to correctly guess at least three of the five odors. Different cards contain different combinations of scents, so there is no answer key to memorize.The Coronavirus Outbreak ›

He estimated that the test could be taken in less than a minute. It is also a manufacturer’s dream, he said: A single printer “could produce 50 million of these tests per day.” Numbers like that, he argued, could make an enormous dent in a country hampered by widespread lack of access to tests that look directly for pieces of the coronavirus.

In their study, Dr. Larremore, Dr. Toomre and their collaborator Roy Parker, a biochemist at the University of Colorado, Boulder, modeled such a scenario using computational tools. Administered daily or almost daily, a smell screen that caught at least 50 percent of new infections was able to quash outbreaks nearly as well as a more accurate, slower laboratory test given just once a week.

Such tests, Dr. Larremore said, could work as a point-of-entry screen on college campuses or in offices, perhaps in combination with a rapid virus test. There might even be a place for them in the home, if researchers can find a way to minimize misuse.

“I think this is spot on,” said Dr. Carol Yan, an ear, nose and throat specialist at the University of California, San Diego. “Testing people repeatedly is going to be a valuable portion of this.”The Coronavirus Outbreak ›

Dr. Toomre is now seeking an emergency use authorization for the U-Smell-It from the Food and Drug Administration, and has partnered with a number of groups in Europe and elsewhere to trial the test under real-world conditions.

Translating theory into practice, however, will come with many challenges. Smell tests that can reliably identify people who have the coronavirus, while excluding people who are sick with something else, are not yet widely available. (Dr. Hopkins pointed to a couple of smell tests, developed before the pandemic, that cost about $30 each and remain in limited supply.) Should they ever be rolled out in bulk, they would inevitably miss some infected people and, unlike tests that look for the actual virus, could never diagnose disease on their own.

And smell loss, like fever, is not exclusive to Covid-19. Other infections can blunt a person’s sense of smell. So can allergies, nasal congestion from the common cold, or simply the process of aging. About 80 percent of people over the age of 75 have some degree of smell loss. Some people are born anosmic.

Moreover, in many cases of Covid-19, smell loss can linger long after the virus is gone and people are no longer contagious — a complication that could land some people in a post-Covid purgatory if they are forced to rely on smell screens to resume activity, Dr. Yan said.

There are also many ways to design a smell-based screen. Odors linked to foods that are popular in some countries but not others, such as bubble gum or licorice, might skew test results for some individuals. People who have grown up in highly urban areas might not readily recognize scents from nature, like pine or fresh-cut grass.

Smell also is not a binary sense, strictly on or off. Dr. Reed advocated a step in which test takers rate the intensity of a test’s odors — an acknowledgment that the coronavirus can drastically reduce the sense of smell but not eliminate it.

But the more complicated the test, the more difficult it would be to manufacture and deploy speedily. And no test, even a perfectly designed one, would function with 100 percent accuracy.

Dr. Ameet Kini, a pathologist at Loyola University Medical Center, pointed out that smell tests would also not be free of the problems associated with other types of tests, such as poor compliance or a refusal to isolate.

Smell screens are “probably better than nothing,” Dr. Kini said. “But no test is going to stop the pandemic in its tracks unless it’s combined with other measures.”

SARS-CoV-2 is following the evolutionary rule book


Natural selection is a powerful force. In circumstances that are still disputed, it took a bat coronavirus and adapted it to people instead. The result has spread around the globe. Now, in two independent but coincidental events, it has modified that virus still further, creating new variants which are displacing the original versions. It looks possible that one or other of these novel viruses will itself soon become a dominant form of sars-cov-2.

Knowledge of both became widespread in mid-December. In Britain, a set of researchers called the Covid-19 Genomics uk Consortium (cog-uk) published the genetic sequence of variant b.1.1.7, and nervtag, a group that studies emerging viral threats, advised the government that this version of the virus was 67-75% more transmissible than those already circulating in the country. In South Africa, meanwhile, Salim Abdool Kalim, a leading epidemiologist, briefed the country on all three television channels about a variant called 501.v2 which, by then, was accounting for almost 90% of new covid-19 infections in the province of Western Cape.

Britain responded on December 19th, by tightening restrictions already in place. South Africa’s response came on December 28th, in the wake of its millionth recorded case of the illness, with measures that extended a night-time curfew by two hours and reimposed a ban on the sale of alcohol. Other countries have reacted by discouraging even more forcefully than before any travel between themselves and Britain and South Africa. At least in the case of b.1.1.7, though, this has merely shut the stable door after the horse has bolted. That variant has now been detected in a score of countries besides Britain—and from these new sites, or from Britain, it will spread still further. Isolated cases of 501.v2 outside South Africa have been reported, too, from Australia, Britain, Japan and Switzerland.

So far, the evidence suggests that despite their extra transmissibility, neither new variant is more dangerous on a case-by-case basis than existing versions of the virus. In this, both are travelling the path predicted by evolutionary biologists to lead to long-term success for a new pathogen—which is to become more contagious (which increases the chance of onward transmission) rather than more deadly (which reduces it). And the speed with which they have spread is impressive.

The first sample of b.1.1.7 was collected on September 20th, to the south-east of London. The second was found the following day in London itself. A few weeks later, at the beginning of November, b.1.1.7 accounted for 28% of new infections in London. By the first week of December that had risen to 62%. It is probably now above 90%.

Variant 501.v2 has a similar history. It began in the Eastern Cape, the first samples dating from mid-October, and has since spread to other coastal provinces.

The rapid rise of b.1.1.7 and 501.v2 raises several questions. One is why these particular variants have been so successful. A second is what circumstances they arose in. A third is whether they will resist any of the new vaccines in which such store is now being placed.

The answers to the first of these questions lie in the variants’ genomes. cog-uk’s investigation of b.1.1.7 shows that it differs meaningfully from the original version of sars-cov-2 in 17 places. That is a lot. Moreover, several of these differences are in the gene for spike, the protein by which coronaviruses attach themselves to their cellular prey. Three of the spike mutations particularly caught the researchers’ eyes.

One, n501y, affects the 501st link in spike’s amino-acid chain. This link is part of a structure called the receptor-binding domain, which stretches from links 319 to 541. It is one of six key contact points that help lock spike onto its target, a protein called ace2 which occurs on the surface membranes of certain cells lining the airways of the lungs. The letters in the mutation’s name refer to the replacement of an amino acid called asparagine (“n”, in biological shorthand) by one called tyrosine (“y”). That matters because previous laboratory work has shown that the change in chemical properties which this substitution causes binds the two proteins together more tightly than normal. Perhaps tellingly, this particular mutation (though no other) is shared with 501.v2.

Golden spike

b.1.1.7’s other two intriguing spike mutations are 69-70del, which knocks two amino acids out of the chain altogether, and p681h, which substitutes yet another amino acid, histidine, for one called proline at chain-link 681. The double-deletion attracted the researchers’ attention for several reasons, not the least being that it was also found in a viral variant which afflicted some farmed mink in Denmark in November, causing worries about an animal reservoir of the disease developing. The substitution is reckoned significant because it is at one end of a part of the protein called the s1/s2 furin-cleavage site (links 681-688), which helps activate spike in preparation for its encounter with the target cell. This site is absent from the spike proteins of related coronaviruses, such as the original sars, and may be one reason why sars-cov-2 is so infective.

The South African variant, 501.v2, has only three meaningful mutations, and all are in spike’s receptor-binding domain. Besides n501y, they are k417n and e484k (k and e are amino acids called lysine and glutamic acid). These two other links are now the subject of intense scrutiny.

Even three meaningful mutations is quite a lot for a variant to have. Just one would be more usual. The 17 found in b.1.1.7 therefore constitute a huge anomaly. How this plethora of changes came together in a single virus is thus the second question which needs an answer.

The authors of the cog-uk paper have a suggestion. This is that, rather than being a chance accumulation of changes, b.1.1.7 might itself be the consequence of an evolutionary process—but one that happened in a single human being rather than a population. They observe that some people develop chronic covid-19 infections because their immune systems do not work properly and so cannot clear the infection. These unfortunates, they hypothesise, may act as incubators for novel viral variants.

The theory goes like this. At first, such a patient’s lack of natural immunity relaxes pressure on the virus, permitting the multiplication of mutations which would otherwise be culled by the immune system. However, treatment for chronic covid-19 often involves what is known as convalescent plasma. This is serum gathered from recovered covid patients, which is therefore rich in antibodies against sars-cov-2. As a therapy, that approach frequently works. But administering such a cocktail of antibodies applies a strong selection pressure to what is now a diverse viral population in the patient’s body. This, the cog-uk researchers reckon, may result in the success of mutational combinations which would not otherwise have seen the light of day. It is possible that b.1.1.7 is one of these.

The answer to the third question—whether either new variant will resist the vaccines now being rolled out—is “probably not”. It would be a long-odds coincidence if mutations which spread in the absence of a vaccine nevertheless protected the virus carrying them from the immune response raised by that vaccine.

This is no guarantee for the future, though. The swift emergence of these two variants shows evolution’s power. If there is a combination of mutations that can get around the immune response which a vaccine induces, then there is a fair chance that nature will find it.