Coronavirus: How worried should we be?

(Cont)
Public health is top of mind, and reason No. 1 why people might be looking to make a move. The coronavirus pandemic has divided the world into “red zones,” which failed to effectively test, quarantine and treat Covid-19 patients, and “green zones,” which performed well under the circumstances and flattened the curve. The daily news tells us which is which—and can help you choose which green zone to move to.

Chances are, you might want to abandon crowded cities. It’s now obvious, if it weren’t before, that staying in big cities can be bad for your health. The density of social contact in urban areas—home to almost 60 percent of the global population—makes them Petri dishes for the spread of contagious diseases. The Covid-19 “attack rate” in New York City was five times the national average. (Similarly, depopulated Eastern European countries have far lower fatality rates from Covid-19
than more densely populated Western Europe.)

Of course, some cities are stickier than others. New York City may have become the Wuhan of the Western Hemisphere, but that doesn’t mean that most New Yorkers won’t stay and lobby officials to be better prepared for future catastrophes, whether viruses or hurricanes.

But other cities might not be so lucky. Milan, Madrid, Tokyo and Seattle are other wealthy, modern cities that have nonetheless become virus hot spots. Their appeal to professionals may diminish given their high cost of living and potential underpreparedness for the next virus wave.

Plus, if you’re going to be regularly quarantined, it might as well be someplace where you can enjoy a nice walk in nature. As Silicon Valley
venture capitalist Balaji Srinivasan put it in a pithy tweet, “Sell city, buy country.”
:- https://www.politico.com/news/magaz...man-migration-251715?utm_source=pocket-newtab

 

Asian American doctors and nurses are fighting racism and the coronavirus
Across the country, Asian Americans have reported a sharp increase in verbal abuse and physical attacks
May 19, 2020 at 4:19 p.m. CDT
Lucy Li tries not to let fear dictate her interactions with patients as she makes the rounds in the covid-19 intensive care unit. But the anesthesiology resident at Massachusetts General Hospital cannot erase the memory of what happened after work at the start of the pandemic.

A man followed the Chinese American doctor from the Boston hospital, spewing a profanity-laced racist tirade as she walked to the subway. “Why are you Chinese people killing everyone?” Li recalled the man shouting. “What is wrong with you? Why the f--- are you killing us?”

Stunned at first, then relieved she was not physically attacked, Li is now saddened and angered by the irony that she spends her days and nights helping save lives. Her work inserting tubes in patients’ airways has grown riskier since the coronavirus emerged — each procedure releasing droplets and secretions that could carry viral particles.

“I’m risking my own personal health, and then to be vilified just because of what I look like,” said Li, 28, wary that one of her patients, too, could harbor such prejudices. “I try not to think about that possibility when I’m at work taking care of patients. But it’s always there, at the very back of my mind.”
Lucy Li outside her home in Boston on May 14. A man shouted a racist rant at Li after she left work one night during the coronavirus pandemic. (Olivia Falcigno/For The Washington Post)
Across the country, Asian American health-care workers have reported a rise in bigoted incidents. The racial hostility has left Asian Americans, who represent 6 percent of the U.S. population but 18 percent of the country’s physicians and 10 percent of its nurse practitioners, in a painful position on the front lines of the response to the coronavirus pandemic. Some covid-19 patients refuse to be treated by them. And when doctors and nurses leave the hospital, they face increasing harassment in their daily lives, too.

Asian Americans have experienced a sharp increase in racist verbal abuse and physical attacks during the pandemic, with the FBI warning of a potential surge in hate crimes against Asians as the coronavirus death toll mounts and stay-at-home orders are lifted.

Sign up for our Coronavirus Updates newsletter to track the outbreak. All stories linked in the newsletter are free to access.

“People are worried about transmission of a disease that they associate with foreignness and Asian faces,” said Grace Kao, a Yale University sociologist. “Nothing erases what we look like.”

There is no comprehensive data measuring anti-Asian bias during the pandemic. An analysis of self-reported incidents by Russell Jeung, chairman of the Asian American studies department at San Francisco State University, shows a steady rise in reports of harassment and assault against Asians since mid-March, with twice as many women than men saying they have been mistreated.
Jeung, who is researching racism and xenophobia amid the pandemic, said a multilingual website set up by his department in a partnership with civil rights groups to document anti-Asian harassment has recorded more than 1,800 reports since its March 19 launch. Victims said they were spat on, stabbed while shopping, shunned for wearing masks and barred from entering ride-hailing vehicles.
Some academic experts on race say President Trump’s rhetoric around the virus and China has contributed to the rise in racial harassment. For weeks, Trump deliberately referred to the coronavirus as the “Chinese virus” despite guidance from public health officials to avoid attaching locations or ethnicity to a disease. He has since tweeted that Asian Americans are not to be blamed for the virus’s spread.

“Words matter. People are making that close association between the virus and Chinese people because he insisted on using that term,” Jeung said.

During a media briefing last week, Trump lashed out at CBS News White House correspondent Weijia Jiang, who is Chinese American, telling her to “Ask China!” after she questioned him on why he insisted on making testing a global competition at a time when so many lives are being lost. Jiang previously tweeted that a White House official had called the virus “the Kung-Flu” to her face.

 

(cont.)
White House adviser Peter Navarro, in an ABC News interview Sunday, accused China of sending “hundreds of thousands of Chinese” to “seed” the coronavirus around the world. And Sen. Ben Sasse (R-Neb.) drew criticism after he blamed the virus’s spread on “thugs in China” in a high school graduation speech over the weekend.

The coronavirus and the long history of using diseases to justify xenophobia

Jeung said he expects harassment and violence against Asian Americans to grow in coming months as states reopen their economies and people return to work, school and public life.

“With the China-bashing and with the economy tanking and more deaths from covid-19, we expect anti-Asian bias to only increase,” Jeung said. “People make automatic assumptions, especially in times of threats, and go into fight-or-flight mode. The fight mode is attacking or harassing Asians, and the flight mode is shunning Asians.”
Former Democratic presidential candidate Andrew Yang has encouraged Asian Americans to step up and “show our American-ness in ways we never have before,” in response to the rise in racist abuse. In a controversial op-ed last month, he called on Asian Americans to be part of the “cure.”

But many Asian Americans felt offended by seemingly having to justify their existence. “It shouldn’t matter if you’re a front-line worker,” said Esther Choo, an emergency-room physician in Portland, Ore., who hosts a podcast on the coronavirus pandemic. “Every time something like this happens, there’s this wave of, ‘But we’re so good, and we don’t deserve this.’ No, you don’t deserve this because you’re human.”

Being a front-line worker didn’t help Li — and when she texted her colleagues to warn them before they left work, one of them responded with her own story of being harassed just a week earlier.


Gem Manalo at Massachusetts General Hospital in Boston on May 14. Manalo was the target of a racist tirade while riding the subway one night during the coronavirus pandemic. (Olivia Falcigno/For The Washington Post)
Gem Manalo, a Mass General anesthesiology resident who is of Chinese and Filipino descent, was riding the “T,” as the subway is called in Boston, across the river to Cambridge for a yoga class in early March when she said a man starting yelling: “F--- China! F--- the Chinese!”
“I was too scared to look at him,” said Manalo, 29. A stranger recorded the incident with her phone and assured Manalo that she would defend her if the man tried to physically harm her.

“He kept saying things like: ‘You people eat bats! Watch my YouTube channel tonight, and I’ll tell the real story.’ He kept saying: ‘F--- China. F--- the Chinese,’ over and over,” Manalo said.

“Here I am in the hospital, working in all these makeshift ICUs,” Manalo said. “We’re all at a loss, too, trying to come up with new protocols to keep everybody safe, and this guy is telling me that I am terrible.”

Hate crimes against Asian Americans have been declining for years. Will the coronavirus change that?

Audrey Li, an internal-medicine resident at Beth Israel Deaconess Medical Center in Boston who plans to specialize in infectious diseases, said she was repeatedly told by a frustrated patient at another hospital to “go back to your country.”

Li, who was born in New Jersey to Chinese immigrant parents, was too shocked to respond and immediately wondered if she had done something wrong. But a white intern told the patient that her comments were unacceptable.
unacceptable.

Audrey Li at Harvard Medical School in Boston on May 14. One hospital patient told Li to “go back to your country." (Olivia Falcigno/For The Washington Post)


“Part of the unsettling piece of racism is you’re never sure if it’s something you as an individual did or if it’s something that’s immutable and larger than yourself,” said Li, 28. “There was a sense of a little bit of guilt and shame for having forgotten what it was like to be marginalized in that way.”

 

(cont)
In Los Angeles County, Hengky Lim, a 44-year-old nurse practitioner from Indonesia, said he approached an ER patient who had a fever and a cough to show him how to put on a mask one night in March. The patient yelled at him and coughed in his face, spit splattering on his plastic face shield. “You know where coronavirus is from? It’s from you people! I don’t want to be seen by you,” Lim recalled the patient shouting. Then the patient walked out of the ER.

In April, when Lim, dressed in a hazmat suit, was treating patients with covid-19 symptoms in a tent outside the main hospital, he said a man who came in with chest pain, difficulty breathing and a persistent cough declined Lim’s assistance and returned to see the nurse who had taken his vitals. That nurse, who was white, later told Lim that the patient said he did not want to be seen by an Asian provider because he thought he had contracted the coronavirus from a Chinese man coughing near him at a store, Lim recalled.

“I asked the nurse, ‘Are you sure it was a Chinese man?’ It’s just stereotyping, assuming everyone who is Asian is Chinese and has coronavirus,” Lim said. He tried to treat the patient anyway, telling him that he was his only choice and that he would take care of him. But the man left after spitting into a cup for the coronavirus test — and did not bother getting the X-ray or EKG that Lim had ordered for him.

 

(cont)
Lim said he had never before encountered such discrimination during his 10 years in nursing, but it has become such a common experience among his Asian colleagues that he thought about quitting.

“Everybody is scared. I’m putting myself out there only to be treated this way. It’s very disheartening,” he said. “We’re not sick. You’re the one who is sick, which is why you are here. And you are exposing us as the health-care provider taking care of you, and we are treated as though we are the ones carrying the coronavirus.”

As the coronavirus spreads, so does online racism targeting Asians, new research shows

This spring in Seattle, Amy Zhang was wearing scrubs, walking to her 13-hour night shift as an anesthesiology resident, when a man began cursing at her a block away from the hospital.

“F--- you, China, for giving us smallpox,” the man shouted at Zhang, the 29-year-old Chinese American doctor recalled. He followed her and continued yelling racial epithets.
Zhang said the encounter shook her, affecting her ability to focus on her work at the start of her shift. “I was not in the best state of mind to help out with patient care,” she said.

And in Southern California, Audrey Sue Cruz, an internal-medicine doctor in Loma Linda, was conducting a telephone visit with a new patient recently when, 15 minutes into the appointment, the woman began grilling the physician on her medical education, work history and ethnicity.

Cruz told the patient that she is Filipina, to which she said the patient replied: “Wow. I can’t believe what your people did. I usually wouldn’t choose an Asian doctor, but you seem nice.”

Cruz quickly ended the visit. The incident inspired her to join more than a dozen other doctors in producing an #iamnotavirus video to help combat the wave of bigotry against Asians.

“We wanted to use our voices as physicians to remove the stigma that’s occurring right now about Asian people being virus carriers,” said Cruz, 30.

She posted the video on Instagram. Then came the comments: “Bat eater.”

Tracy Jan
Tracy Jan covers the intersection of race and the economy for The Washington Post, a beat she launched in December 2016. She previously was a national political reporter at the Boston Globe.
:- https://www.washingtonpost.com/busi...ican-discrimination/?utm_source=pocket-newtab

 

Why the Race to Find Covid-19 Vaccines Is Far From Over
Despite the promising news from Pfizer and Moderna, other efforts – which may be even more effective – continue around the world
The Guardian/ Laura Spinney

While everyone celebrated this month’s news that not one but two experimental vaccines against Covid-19 have proved at least 90% effective at preventing disease in late-stage clinical trials, research into understanding how the Sars-CoV-2 virus, which causes Covid-19, interacts with the human immune system never paused.
There are plenty of questions still to answer about the Pfizer/BioNTech and Moderna vaccines: how well will they protect the elderly, for example, and how long for? Which aspects of the immune response that they elicit are protective and which aren’t? Can even better results be achieved, with vaccines that target different parts of the immune system?
We are likely to need several Covid-19 vaccines to cover everyone and as a contingency, in case the virus mutates and “escapes” the ability of one vaccine to neutralise it, a real possibility in light of the discovery of an altered form of Sars-CoV-2 infecting European mink. But we also need better methods of diagnosing and treating the disease. The recent suspension of two major vaccine trials due to serious adverse events is a salutary reminder that there’s much still to learn and a pandemic, while no one would wish for one, provides scientists with a golden opportunity for learning.

Like most Covid-19 vaccine candidates, the Pfizer and Moderna vaccines are injected into the muscle, from where they enter the bloodstream and stimulate the production of antibodies to Sars-CoV-2 (specifically to the protein that forms the spikes covering its surface). But antibodies are only one component of the body’s adaptive immune response, which develops over time, in response to invasion by a virus or other pathogen. There is also innate immunity, which we are born with and that is mobilised instantly upon infection, but is not tailored to any specific pathogen. “There are a lot of moving parts to this,” says immunopharmacologist Stephen Holgate, of the University of Southampton in the UK, who wonders why scientists have focused on so few of them.

Holgate is one of the founders of Synairgen, a University of Southampton spin-off company that has been testing inhaled interferon-beta, an important innate defence that works by shutting down viral replication, as a treatment for Covid-19. A major international study backed by the World Health Organization, called Solidarity, showed that interferon-beta was not effective in treating hospitalised patients, but more recently Synairgen has published the results of a small pilot study suggesting that given in patients with milder disease – and inhaled rather than injected under the skin – it enhanced recovery.

“The reason bats are able to harbour these viruses in such large numbers is that they have such a strong interferon response,” Holgate says. “That is why they don’t develop disease.” Synairgen is now testing whether interferon-beta can prevent hospitalisation in patients who inhale it soon after testing positive, at home. If the approach works, he says, the advantage is that it will continue to do so even if the virus mutates, since interferon’s action does not depend on the structure of the virus.

Another immune response that has received a lot of attention in the context of Covid-19 is that of T-cells. Along with B-cells, which generate antibodies, T-cells form part of the adaptive immune system and they perform two main functions: they help B-cells do their job and they kill infected cells. Both B- and T-cells retain a memory of past infections, meaning they are mobilised more quickly when a pathogen appears for a second or subsequent time.

In May, US researchers reported that T-cells extracted from human blood samples taken before 2019, and exposed to Sars-CoV-2, showed a memory for coronavirus infection. This suggested that previous exposure to different coronaviruses, such as those that cause the common cold, might be sufficient to prime T-cells and raised hopes that they could protect against Covid-19. Those hopes were bolstered by a report of people fighting off infection even though they developed only a T-cell response and no antibodies, though the number of patients in that study was small and the evidence therefore hard to interpret. Lockdown sceptics pointed to these studies as evidence that more of the population was protected against Covid-19 than was thought, but some immunologists say they did so prematurely.

As Akiko Iwasaki of Yale University in the US explains: “T-cells cannot prevent infection, they can only respond when there is an infection.” So although they could potentially reduce the severity of the disease, they can’t stop its transmission between people. Also, there is still no proof that the T-cell response is helpful. “It’s likely that both antibodies and T-cells are important in protection, but we have zero evidence so far for protection of any kind,” says immunologist Zania Stamataki of the University of Birmingham in the UK.


Obtaining that evidence will involve seeing how people either exposed to the virus naturally or vaccinated against it respond upon reinfection. Vaccine trials could provide such evidence, as could a number of studies of the correlates of protection in natural infection. Iwasaki’s group, for example, is comparing the immune responses of unexposed, sick and recovered individuals, while virologist Florian Krammer of the Icahn School of Medicine at Mount Sinai, New York City, and colleagues are tracking those responses longitudinally, in thousands of people exposed naturally over time. Then there are the so-called challenge trials that are due to be launched by Chris Chiu of Imperial College London and colleagues in January.

In the first stage of these trials, about 30 young, healthy individuals will have their immune status measured before and after deliberate exposure to Sars-CoV-2. The trials will generate data on immune responses in the blood, but also, because the virus will be delivered via the nose, on any local immune response that develops there. Both antibodies and T-cells are made at the body’s mucosal membranes, including those lining the airways, as well as in the blood, and this mucosal immunity is causing excitement among some scientists, though vaccine makers have so far paid it scant attention.

 

(cont).
“The virus comes in and it lands on your mucosal surfaces,” explains Krammer. “If it’s neutralised right there, it’s game over.” Unable to replicate and penetrate deeper into the body’s tissues, the virus is prevented from causing not only disease but also infection, meaning the person can transmit it no further. It’s not yet clear if the Pfizer and Moderna vaccines block transmission, as well as preventing disease, but a vaccine that did so could bring the pandemic to an end sooner. And it could do it without the need for an injection – just by using a nasal spray or inhaler.

Antibodies come in different forms that vary according to their biological properties and the tissues in which they are expressed. Like the Pfizer and Moderna vaccines, most Covid-19 vaccines in development elicit IgG antibodies in the blood, but the main antibody secreted in the upper respiratory tract, essentially the nose and throat, is IgA.


In June, in a study that has now been accepted for publication in a peer-reviewed journal, a French group detected IgA antibodies in the blood of Covid-19 patients as early as a day after the onset of their symptoms. IgA levels peaked three weeks later, a week before IgG peaked. Then in August, a Canadian group reported the same finding in saliva. “The IgA response comes up early and dissipates quickly, whereas the IgG response persists,” says immunologist Jennifer Gommerman of the University of Toronto, one of the lead authors on that study.

The short duration of that IgA response might not matter as much as the fact that it peaks early – within a day or two of the innate response. The adaptive immune system kicks in if that innate response fails – it’s the second line of defence – but if you could enhance that early IgA response you could still block infection and prevent the person from feeling ill at all. Researchers have some reason to hope this may be possible.

IgA occurs in different forms at the mucosal membranes and in the blood. In the blood, it circulates singly, while at the membranes lining the airways it is secreted in pairs or even clusters. There is some evidence that doubled up, IgA antibodies’ capacity to neutralise the virus increases significantly, probably because each pair has twice as many binding sites at which to capture the invader. “If you have an antibody on its own, it works pretty well,” says Guy Gorochov of the Sorbonne University in Paris, who led the French study of IgA. “If you have a pair of them, it is far more effective.”

An inhaled vaccine against flu that elicits a local immune response in the airways already exists and there are Covid-19 vaccines in development that do the same, though they are a long way from clinical trials. Researchers are intrigued by the possibility that, besides antibodies, such a vaccine could also stimulate a kind of T-cell that is produced in the lining of the respiratory tract, called tissue-resident memory T-cells, and that these could contribute to shutting down infection rapidly. What’s more, measuring this local response could give an early and accurate indication of a person’s capacity to fight off the disease. “The work we’ve done in the past, with other respiratory viruses, suggests that IgA in the nose is often a much better correlate of protection than circulating antibodies,” says Chiu.

There’s a lot more work to be done before the human immune response is fully leveraged to fight Covid-19 and what is learned in the context of this disease could be applied to others, especially when it comes to therapies that modify the human immune response rather than the virus. For now, though, most experimental vaccines and therapies target antibodies, which are virus-specific and one type of antibody, IgG, in particular. One piece of good news, where these are concerned, is that several studies, including Gommerman’s and Krammer’s, have now demonstrated that IgG levels remain high for up to eight months after infection. The same durability of antibody response has yet to be demonstrated for any vaccine, but these findings bode well.

The best news of all is that at least two vaccines now exist that seem to protect us against Covid-19 and that the chances are high that some of the most vulnerable people in the world will benefit from them within months. It remains an extraordinary and unprecedented feat to have built such a vaccine, and shown it to be safe and effective, before the disease they protect against is one year old – and before the pandemic is over.
:- https://getpocket.com/explore/item/...nes-is-far-from-over?utm_source=pocket-newtab

 

3 Questions And The Emerging Answers About COVID-19 Vaccine Protection

January 18, 202111:50 AM ET



Richard Harris




Researchers are making progress in understanding the human immune response to SARS-CoV-2, the virus that causes COVID-19, and the vaccine to prevent the disease.

Christoph Burgstedt/Science Source
As the COVID-19 vaccine rolls out, three big questions loom. First, can someone who has been vaccinated still spread the disease? Second, will the vaccine remain effective as the virus itself evolves? And third, how long will the vaccine's protection last?


Answers to these questions lie in our immune systems. And the answers aren't straightforward because our immune systems are both remarkably adept and remarkably challenging to predict.


Let's start with the first question, about whether people who are vaccinated can still spread the disease. Marion Pepper, an immunologist at the University of Washington, says that's not just an open question for this vaccine, but for vaccines in general.


"I think it's hard to say because we're constantly being bombarded by different pathogens and we don't know when your immune system is responding," she says. We may have infections that don't make us sick, so we never know about them. But we could be spreading disease.


When a person is infected – or inoculated with a vaccine – the immune system gears up to produce antibodies that specifically target the virus. Over time, those antibodies naturally wane. But the immune system still holds a memory of the virus, and if it ever shows up again, cells spring into action and start to gear up a new batch of antibodies. However, that process can take three to five days.
In the meantime, a virus can potentially start to replicate in the body.

"It's a bit of a race between the immune system and the virus," says Dr. Michel Nussenzweig, a Howard Hughes Medical Institute investigator at the Rockefeller University.

If the immune response kicks in quickly, little virus would be produced. Your ability to spread disease "is really a function of how much virus you're producing," Nussenzweig says.

It seems likely a person's immune system will win that arms race, but scientists don't have the data yet to say that with confidence. That's why people who have been vaccinated are still supposed to wear a mask and take other precautions – until that gets sorted out.

 

(cont.)
Another wild card here is that your lungs and nasal passages contain a population of so-called T cells, which are primed to identify cells that have been infected with a virus. This type of T cell is much harder to study since it stays inside tissues, so scientists studying blood samples don't end up seeing it.


Since these T cells are primed to react immediately, they might also help bridge the gap between the time you get infected and the time that your immune system can mount a full response with antibodies.


"In influenza, those T cells that are embedded in the tissue can have a dramatic effect of limiting the infection," says Stephen Jameson, an immunologist at the University of Minnesota Medical School. But whether they perform as well in COVID-19, "we don't really know enough yet," he says.


The second question, about whether the vaccine will remain effective even as the virus evolves, is harder to answer. Scientists thus far aren't too concerned about the current strains of the virus that are spreading globally – vaccines will apparently still work against them. But the virus will continue to morph, with uncertain consequences.


"Even though everyone is obviously concerned about a virus evolving, your memory B cell responsiveness also evolves over time," Pepper says.


Memory B cells are an important component of the immune system because they remember an infection. These lurk in your bone marrow and are ready to morph into antibody-producing cells if the virus they "remember" reappears in your body.


But they don't simply remember one specific antibody that has worked against a virus in the past. They can also randomly generate new antibodies that are similar and that may be more effective against a strain of virus your body has never seen.


"It's pretty much the only time in the body where a mature cell introduces mutations intentionally into the DNA," Pepper says.


But remarkable as this system is, it does have limits. Viruses that undergo significant changes from one year to the next, such as the flu, can outmaneuver this system. That's why you need a new flu shot every year. The coronavirus that causes COVID-19 mutates much more slowly than the flu, but it's not yet clear whether memory B cells will be adaptable enough to keep the virus permanently in check.

 

(cont.)
Finally, is the question of how long a vaccine will last.
In some instances, your immune system can have a very long memory.

"Some natural infections can give you lifelong immunity," Jameson says. "You only get it once, and you're protected for the rest of your life."


Vaccines mimic a natural infection to trigger an immune response. But vaccines may require a boost to keep that immunity strong. The memory B cells that target the coronavirus that causes COVID-19 may not have the staying power of the cells that protect us from the measles, for instance. So far, scientists have observed that these memory B cells have persisted for many months following a case of COVID-19, but it's too early to say anything about whether they will eventually fade.


"The good thing is there would be the opportunity that if it turned out there was some waning of the immune response," Jameson says, "then, like many other vaccines, maybe ... you get another booster after a year or something."


These questions reflect how much scientists have come to understand about our immune system in recent years. COVID-19 is also illuminating what we still don't know about how the immune system defends us from infectious germs.


"It's been very interesting to watch this unfold in real time," Pepper says, "because we're learning so much about this virus and the immune response to it in a way that we've never done previously."


You can contact NPR science correspondent Richard Harris at rharris@npr.org.
:- https://www.npr.org/sections/health-shots/2021/01/18/957322501/3-questions-and-the-emerging-answers-about-covid-19-vaccine-protection?utm_source=pocket-newtab

 

Worrisome New Coronavirus Strains Are Emerging. Why Now?
Across the globe, SARS-CoV-2 is evolving ways to evade the immune system and become more infectious. Blown pandemic response plans are to blame.
Toward the end of last year, doctors in Nelson Mandela Bay, a city of about 1 million people in the Eastern Cape of South Africa, started to see something alarming. The city had been hit by a tsunami of Covid-19 cases in June and July, swamping hospitals and leading to thousands of deaths. That wave began to subside as winter turned to spring in the southern hemisphere. But starting in November, hospitals in the city and its surrounding province began to fill up with Covid-19 patients again—this time twice as fast they had during the first surge.

To figure out what was going on with the steep uptick in new cases, doctors at those hospitals enlisted the help of Tulio de Oliveira, a geneticist and bioinformatician at the University of KwaZulu-Natal in Durban who leads a national network of sequencing labs. His team began piecing together the genomes of the coronavirus that had caused each person’s infection. For months, these researchers had been periodically doing similar genomic surveillance work to keep tabs on the dozens of strains of SARS-CoV-2 that were circulating around the country, looking for any problematic mutations in the virus’s spike protein. Eight months into the pandemic, in 99 percent of the more than 1,500 genomes they’d sequenced, they’d only found one such mutation. De Oliveira was in the process of submitting those findings to a journal.

Then, on December 1, the first results came back from Nelson Mandela Bay.
In each of the 16 samples gathered from 15 clinics around the city, the viruses all possessed a near identical constellation of mutations unlike any that had ever before been seen in South Africa. And eight of those mutations were in the spike protein. “Literally the day before I had written, ‘The spike genome in South Africa is very stable,’” de Oliveira told WIRED in an interview. “Then I saw this new cluster and I thought, ‘Wow, that has changed.’”

 

(cont.)
He walked upstairs, to the office of South Africa’s corollary to Anthony Fauci, an epidemiologist named Salim Abdool Karim, to tell him the news. Days later, they alerted the World Health Organization. Now on the lookout, scientists in the United Kingdom soon discovered one of those mutations spreading in the southeast part of Britain. A few weeks later, an eerily similar cluster of genetic changes surfaced among travelers from Brazil. But neither was a case of jet-setters seeding a single new strain around the world. Analyses of global coronavirus genome databases showed that these were in fact three distinct versions of the virus—three distantly related branches of the SARS-CoV-2 family tree that had independently acquired some of the same mutations despite emerging on three different continents.

That pattern is what scientists refer to as “convergent evolution,” and it’s a sign of trouble ahead.

All viruses mutate. They are, after all, just autonomous bits of protein-encased, self-replicating strings of code equipped with imperfect internal spell-checkers. Make enough copies and there are bound to be mistakes. Coronaviruses actually make fewer mistakes than most. This one, SARS-CoV-2, evolves at a rate of about 1,100 changes per location in the genome annually—or about one substitution every 11 days.

The predictable pace at which the coronavirus’s genetic building blocks shift around can be detected by genomic sequencing, which allows scientists to identify new strains and follow them as they spread through a population or fade away. For most of 2020, those random changes didn’t have much of an effect on the way the virus behaves. But recently, three notable mutations have begun to show up alone or in combination with each other. And everywhere they do, these versions of the virus tend to quickly outcompete other circulating strains.

 

(cont.)
“That suggests there’s an advantage to these mutations,” says Stephen Golstein, an evolutionary virologist who studies coronaviruses at the University of Utah. “Every SARS-CoV-2 variant ‘wants to be more transmissible,’ in a sense. So the fact that so many of them are landing on these mutations suggest there could be a real benefit for doing so. These different lineages are essentially arriving at the same solution for how to interact more efficiently with the human receptor, ACE2.”

Like any virologist, Goldstein is hesitant to anthropomorphize his subjects. Viruses don’t have dreams and desires. They’re intelligent micromachines programmed to make as many copies of themselves as possible. But one way to do that is to increase their odds of invading new hosts. SARS-CoV-2 does that by guiding the array of spike proteins that coat its exterior toward a protein called ACE2 that sits on the outside of some human cells. The spike is encrusted in sugars which camouflage the virus from the human immune system, except for the very tip, known as the receptor binding domain, or RBD for short. This exposed section is the part that latches onto ACE2, changing the receptor’s shape—like a key rearranging the tumblers inside a lock—and allowing the virus to enter the cell and start replicating.

The mutations that have scientists so worried all occur in that little exposed bit of spike. And now researchers are racing to figure out how each of them might be giving SARS-CoV-2 some new tricks.

There’s N501Y, a mutation that occurs in all three variants, which replaces the coronavirus’s 501st amino acid, asparagine, with tyrosine. Studies in cells and animal models suggest that the change makes it easier for SARS-CoV-2 to grab onto ACE2, which is one hypothesis for why the variant has been, at this point, pretty convincingly associated with increased transmission. The best evidence for that so far has come out of the UK, which is doing more genomic sequencing than any other country in the world. Scientists there estimate that the UK variant, alternatively known as B.1.1.7, is between 30 and 50 percent more infectious than other circulating strains.

In Ireland, it became the dominant version of the virus in just a few weeks, and it has since spread to more than 60 countries, including the US. As of Tuesday, the US had detected 293 cases of the UK variant, according to data from the US Centers for Disease Control and Prevention. The agency estimates it will become dominant in the US by March.

A Brazilian variant, also called P1, and the South African one, sometimes called B.1.351, also have a second and third mutation in common: K417T and E484K. At this moment, scientists know more about the latter. It changes an amino acid that was negatively charged to one that’s positively charged. In variants without this mutation, that section of the RBD sits across from a negatively charged stretch of ACE2, so they repel away from each other. But the E484K mutation reverses that charge, making them snap tightly together instead.

On Monday, Minnesota reported the US’ first case of the Brazil variant, but so far no cases of the South African variant have yet been confirmed in the US.

Scientists at the Fred Hutchinson Cancer Research Center found that E484K might be the most important alteration when it comes to enhancing the virus’s ability to evade immune defenses. In lab experiments, they observed that antibodies in the blood of recovered Covid-19 patients were 10 times less effective at neutralizing variants possessing the E484K mutation. In a separate study, some of De Oliveira’s colleagues tested the blood from Covid-19 patients who fell ill in South Africa’s first wave, and they found that 90 percent of them had some reduced immunity to the new E484K-containing variant. In nearly half of the samples, the new variant escaped the preexisting antibodies completely. Another study by another South African colleague, this time using live virus, found similar results. (All are being shared as preprints—neither has yet been peer-reviewed, as has become common in the age of Covid.)

 

(cont.)
“All the evidence is starting to point in the same direction,” says de Oliveira. “We have a virus that is much less neutralized by convalescent plasma.” It’s still too soon to tell what that means in the real world. True reinfections are notoriously difficult to pin down. Scientists have to sequence samples taken from the first bout of illness and the second, and then compare the genetic signatures to determine if a different viral variant is responsible for each infection. De Oliveira says his group is in the process of doing that right now, and they’re finding many instances of what appear to be real reinfections with the South African variant. That data is not yet published. And until they sequence more samples, they can’t say whether B.1.351 is causing more reinfections than previous versions of the virus, which would be a sign that herd immunity might be much farther off than previously thought.

Researchers in Brazil have also found evidence of at least one reinfection with the new P1 lineage, but data there is even sparser. Some reinfections are to be expected, says William Hanage, an infectious disease epidemiologist at the Harvard T. H. Chan School of Public Health. The important thing is whether there are more reinfections with the new variant than the models would expect.

Still, that these worrying mutations are all cropping up in the same region of the spike protein is not a coincidence, says Goldstein. Of all the places in the coronavirus’s genome, the RBD is the least stable. “That’s because, historically, it’s been under the most evolutionary pressure to change,” he says. It may feel like the Covid-19 pandemic has been happening forever. But in evolutionary terms, it’s been but a blink.

Before SARS-CoV-2 crossed into humans, it had been circulating inside bats for millions of years. And when scientists began taking a closer look at the bat version of ACE2, they found a staggering diversity of the gene that codes for that protein. What they were seeing were the genetic scars of an evolutionary arms race. Bat populations had lived with SARS-CoV-2 for long enough that their ACE2 receptors had started changing—morphing in shape so that they became harder for the virus to grab onto. And in turn, SARS-CoV-2 had evolved to try to fit into those new shapes. Eventually, one of those descendants looked enough like the human ACE2 receptor that it could make the cross-species leap (with perhaps an intermediary host in there somewhere).

There are two major evolutionary forces driving diversification of the spike protein: interacting with ACE2, and getting clobbered by neutralizing antibodies. In the human population, a year isn’t long enough for new versions of ACE2 to crop up and be passed on to a new generation of people. And ACE2 plays a key role in regulating blood pressure, wound healing, and other essential functions, so any genetic changes that impair its ability to do those things would likely not get very far, even if they made it more difficult for the coronavirus to start an infection.

So if the evolution of the ACE2 receptor can’t rescue us in the short term, that leaves the body’s immune system, and the armies of cells that orchestrate ejecting any unwanted visitors from it. Many pathogens mutate their proteins toward new shapes to avoid being recognized by the antibodies that would normally adhere to them, blocking their entry into cells. That’s called antigenic drift. And that’s what some scientists think drove the emergence of the Brazil and South African variants.

 

(cont.)
In a study recently posted as a preprint and not yet formally reviewed, Theodora Hatziioannou, a virologist at Rockefeller University in New York, and her colleagues described creating a pseudo-coronavirus carrying a nonvariant version of the spike protein. They grew it in the presence of individual antibodies they had extracted from the blood of people who had received one of the two FDA-authorized Covid-19 vaccines, one from Pfizer/BioNTech and one from Moderna. Some antibodies spurred the pseudo-SARS-CoV-2 to acquire the E484K mutation. Others nudged it toward K17T or N501Y.

They tried the experiment again with no antibodies present, and none of these three mutations—the ones in the triple-variant threat—evolved the same evasive maneuvers. “This data shows that these mutations accumulating in the spike protein are antibody escape mutations,” says Hatziioannou. “As soon as you add a specific antibody, you see specific mutations.”

Her group used blood donated by immunized people. But the vaccines have not been rolled out widely enough to be exerting significant evolutionary pressure on the general population. So the obvious question is: Where did the virus encounter these antibodies?

Hatziioannou and others think there are clues to be found in the genomes of viruses that took up long-term residence in the bodies of immunocompromised Covid patients. Up until a few weeks ago, the prevailing theory was that escape mutations could have emerged in people with chronic infections, who might be receiving monoclonal antibody treatments or convalescent plasma, and therefore supercharging the selective pressures the virus has to contend with.

Goldstein has a simpler explanation, one that’s beginning to get more traction in the scientific community. The convergent evolution of wilier versions of the virus might just be a consequence of so many poorly managed government pandemic responses, which didn’t marshal sufficient resources or inspire the kind of collective action required to not just crush the initial curve, but keep it crushed. “The fact that we lost control in so many places in the fall allowed for the ballooning of this incredibly huge viral population size,” says Goldstein. That created the opportunity for that many more mutations to happen, and in some places, the right circumstances for some particularly insidious ones to get selected.

Hanage put it this way to reporters last week: “The strategy here and elsewhere has been to try and control the level of transmission that doesn’t require very severe restrictions, but also doesn’t allow the virus to go exponential and overload health care systems.” But the problem with that approach is that it still gives the virus plenty of opportunities to mutate, and in so doing, change its behavior. If those changes make it spread faster or give it an edge against treatments and vaccines, that balancing act falls apart. “It tips you from a point where you’re capable of dealing with it to a point where you’re not,” he continued.

Hannage pointed to what’s going on right now in Manaus, a city in the Brazilian Amazon where a devastating surge in May left up to 70 percent of its residents infected with SARS-CoV-2, according to an analysis published this month in Science. Doctors and researchers there assumed the city was safe for a while—that herd immunity, or close to it, had been reached. But this month, the Manaus public health system collapsed again under a new Covid crush, leaving hospitals scrambling to get enough oxygen for its mass of patients. “I’m not yet aware of any evidence to suggest that the P1 variant is more likely to infect or reinfect people,” said Hanage. “But the fact that this is happening in a place that had previously been exposed to such high amounts of transmission is extremely worrying, very worrying indeed.”

 

(cont.)
Scientists may never get a clear answer to exactly where and under what conditions these new variants emerged. But de Oliveira isn’t so sure it matters. “The one thing we know for sure is that if you keep the virus circulating long enough, it will develop escape mutations,” he says.

The much more pressing question, then, is to what degree will such mutations affect efforts to vaccinate our way out of the pandemic?

A spate of recent studies, released as preprints have mostly good—and some mixed—news on that front. Lab tests conducted by scientists at BioNTech showed that their vaccine should still work just as well against B.1.1.7, the UK variant.

In their recent preprint, Hatziioannou’s group also took a closer look at B.1.351, the South African variant. They found that antibodies taken from people vaccinated with either Pfizer/BioNTech or Moderna’s shots were up to three times less effective at neutralizing the pseudoviruses carrying the mutations found in B.1.351, compared to ones without those genetic changes in the spike protein. But since those vaccines have such a high starting efficacy—over 90 percent—there’s still a lot of wiggle room.

 

(cont.)
On Monday, Moderna scientists and their partners at the National Institutes of Health released the not-yet-peer-reviewed results of their own lab experiments using blood from people who had received the company’s vaccine. Although antibodies from immunized people fended off the UK variant just fine, they found, the South African variant caused some issues. Against that strain, the neutralizing power of the antibodies induced by Moderna’s vaccine was reduced six-fold, though they still functioned at levels believed to be effective.

In a statement, Moderna CEO Stéphane Bancel said that he is confident the company’s vaccine should still be protective against the newly detected variants, but that “it is imperative to be proactive as the virus evolves.” To that end, Moderna’s scientists are retooling the company’s mRNA sequence to more closely mimic the most significant mutations and plan to test it as an additional booster shot in clinical studies later this year.

“We shouldn’t panic yet, but we should be careful. This is a warning,” says Hatziioannou. “If the virus continues to accumulate mutations in its spike protein, we run the risk of the efficacy of vaccines diminishing further.”

Vaccines target the whole spike protein, and they have been shown to make lots of different antibodies that bind to different parts of it. So losing the ones that block the RBD isn’t game over. There are plenty of built-in redundancies. But it leaves more work for the rest of the immune system. It’s like trying to kick out a home invader after you’ve left the front door unlocked. It gives the virus a little leg up. “The most important antibody targets do happen to be the most variable parts of the spike protein,” says Goldstein. “That’s why we’re locked in this evolutionary battle with the virus.”

 

(cont)
With these new variants showing signs of being better at spreading and eluding both natural immune defenses and treatments like monoclonal antibodies and convalescent serum, the race is on to vaccinate as many people as possible in the shortest time frame. At least in the US, the last mile challenges with getting ultra-cold, two-shot vaccines into people’s arms are proving so problematic that the Biden administration has proposed creating 100 new mass vaccination sites across the country.

That’s good. But scientists like Hanage are still worried that if governments and societies don’t do enough to slow the speed of infections soon, more dangerous mutations will almost certainly emerge. “The fact that it’s happened three times already means we can expect it to continue happening,” he said during last week’s press briefing.

If you ask de Oliveira, he’ll tell you that it is already happening, and much faster than anyone realizes. “I am quite convinced that there are dozens, if not hundreds, of variants with similar mutations emerging around the world right now,” he says. He believes that the only reason that South Africa and the UK picked them up first is because their governments invested in comprehensive surveillance networks. That’s why he thinks nations need to stop useless travel bans and start ramping up testing, sequencing, contact tracing, and vaccination efforts. It may take years to inoculate enough people to curb the coronavirus’s evolution. Buying time until then means doing everything that has so far proven effective at limiting its chances of finding new hosts, and new opportunities to mutate: social distancing, mask-wearing, avoiding crowds, and increasing ventilation. “The important thing,” says de Oliveira, “is to realize we have to drive transmission to almost zero if we are to avoid new variants emerging in the future.”
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If Covid-19 Did Start With a Lab Leak, Would We Ever Know?
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What You Can Do to Avoid the New Coronavirus Variant Right Now

By Tara Parker-Pope

• Published Jan. 19, 2021Updated Jan. 28, 2021

It’s more contagious than the original and spreading quickly. Upgrade your mask and double down on precautions to protect yourself.
New variants of the coronavirus continue to emerge. A few have caused concern in the United States because they are so contagious and spreading fast. To avoid them, you’ll need to double down on the same pandemic precautions that have kept you safe so far.

The variant known as B.1.1.7., which was first identified in Britain has the potential to infect an estimated 50 percent more people, and researchers have begun to think that it may also be slightly more deadly. The Centers for Disease Control and Prevention has predicted that this variant could become the dominant source of infection in the United States by March. A variant first reported in South Africa has found it’s way to South Carolina. And scientists are studying whether a variant with a different mutation, and first found in Denmark, along with one identified in California, have caused a surge of cases in California.

The new variants appear to latch onto our cells more efficiently. (You can find a detailed look inside one of the variants here.) The change suggests it could take less virus and less time in the same room with an infected person for someone to become ill. People infected with the variant may also shed larger quantities of virus, which increases the risk to people around them.

“The exact mechanism in which it’s more transmissible isn’t entirely known,” said Nathan D. Grubaugh, assistant professor and epidemiologist at the Yale School of Public Health. “It might just be that when you’re infected, you’re exhaling more infectious virus.”
So how do you avoid a more contagious version of the coronavirus? I spoke with some of the leading virus and infectious disease experts about what makes the new variant so worrisome and what we can do about it. Here’s what they had to say.
How can I protect myself from the new coronavirus variant?
The variants spread the same way the coronavirus has always spread. You’re most likely to contract the virus if you spend time in an enclosed space breathing the air of an infected person. The same things that have protected you from the original strain should help protect you from a variant, although you may need to be more rigorous. Wear a two- or three-layer mask. Don’t spend time indoors with people not from your household. Avoid crowds, and keep your distance. Wash your hands often, and avoid touching your face.