The United Kingdom on Wednesday granted temporary authorization for emergency use of the Covid-19 vaccine developed by Pfizer and BioNTech to adults age 16 and older, with the first 800,000 doses of the two-dose vaccine slated to be offered in the country next week.

This makes the UK the first country to approve the Pfizer/BioNTech mRNA-based vaccine and the first government approval of a vaccine backed by a clinical trial. (Some countries like Russia and China began administering their Covid-19 vaccines before completing large-scale trials.) It’s also the fastest a vaccine has ever gained approval, albeit on a temporary basis.

“I’m confident now, with the news today, that from spring, from Easter onward, things are going to be better,” said UK Health Secretary Matt Hancock during a press conference. “And we’re going to have summer next year that everyone can enjoy.”

The UK’s health regulator, the Medicines and Healthcare Products Regulatory Agency (MHRA), granted the temporary authorization shortly after Pfizer and BioNTech reported in November that their Covid-19 vaccine was 95 percent effective. Though this is a temporary authorization, the MHRA is conducting a rolling review of vaccine trial data as it comes in and may grant full approval at a later date. In contrast, the US Food and Drug Administration is evaluating vaccines based on completed studies, which increases the length of the approval process.

The UK government reached a deal with Pfizer and BioNTech to purchase 40 million doses of the vaccine through 2021 — enough for 20 million people — mainly shipped from Pfizer’s manufacturing plant in Puurs, Belgium.

“This authorization is a goal we have been working toward since we first declared that science will win, and we applaud the MHRA for their ability to conduct a careful assessment and take timely action to help protect the people of the U.K.,” said Pfizer CEO Albert Bourla, in a statement.

The UK has been one of the most severely afflicted countries during the Covid-19 pandemic, with 1.6 million reported infections and almost 60,000 deaths in a population of 66 million. The government recently imposed a second national lockdown as cases spiked; restrictions on movement and which businesses can stay open may begin to relax this week as the number of new cases declines. But with winter approaching, the risk of more Covid-19 spread in the UK remains high.

The UK is prioritizing older adults to receive a Covid-19 vaccine

With limited doses of the Pfizer/BioNTech vaccine to give out for the time being, the UK is establishing several priority tiers for Covid-19 immunization.

The country’s Joint Committee on Vaccination and Immunisation (JCVI) on Wednesday laid out guidelines for administering the vaccine based mainly on age. The top priority is residents and workers at care homes for older adults, a ranking based on the number of vaccinations that would be needed in each tier to prevent one death, not necessarily risk of exposure.

That’s why health workers, who will be at the front of the line in the US, are not in the top tier in the UK, even though they may be encountering the virus more frequently. “As the risk of mortality from COVID-19 increases with age, prioritisation is primarily based on age,” according to the guidelines.

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The committee divided its overall priority list into nine groups. “It is estimated that taken together, these groups represent around 99% of preventable mortality from COVID-19,” according to the JCVI guidelines.

But the guidelines also note that vaccine deployment strategies may have to shift to address concerns like mitigating health inequalities and logistical challenges. The latter is particularly important for the Pfizer/BioNTech vaccine because it has some of the most stringent cold storage requirements of any Covid-19 vaccine candidate: temperatures of minus 70 degrees Celsius (minus 94 degrees Fahrenheit) or lower. While Pfizer and BioNTech are developing shipping containers that can maintain these temperatures for 30 days, it’s likely that the first facilities to receive it will be major health facilities that already have freezers.

Recipients will have to receive the vaccine as two doses spaced 21 days apart, so rigorous patient tracking will be needed as well.

The US is now waiting on emergency approval for two Covid-19 vaccines

Advisers to the Centers for Disease Control and Prevention this week voted on US guidelines for vaccine approval. The recommendations from the Advisory Committee for Immunization Practices stated that health workers and residents of long-term care facilities should be up first for a Covid-19 vaccine. That health workers are in the top tier stands in contrast to the guidelines issued by the UK.

Establishing these priorities is all the more critical now that a vaccine is poised to begin distribution in the US in weeks. Pfizer and BioNTech have also applied for an emergency use authorization (EUA) in the US from the FDA for their Covid-19 vaccine. The FDA is meeting on December 10 to discuss their vaccine. This week, Moderna, another mRNA Covid-19 vaccine developer, also applied for an EUA.

If granted, these emergency approvals would mark the fastest vaccine development timeline ever, an amazing feat against an unprecedented pandemic. But Covid-19 cases are continuing to rise across the US, and it will still be a few more months before there is widespread access to a vaccine.

As if the Covid-19 pandemic wasn’t bad enough, America is also seeing a surge in homicides this year.

A new report, by the Council on Criminal Justice, found homicides have increased sharply this year across 21 US cities with relevant data: “Homicide rates increased by 42% during the summer and 34% in the fall over the summer and fall of 2019.” Other data, from crime analyst Jeff Asher, found murder is up 36 percent throughout the year so far, compared to the same period in 2019, in a sample of 51 US cities. A preliminary FBI report also found murders up 15 percent nationwide in the first half of 2020.

The increase in homicides is large and widespread enough to raise serious alarms for criminologists and other experts. So what’s going on?

Some experts have cited the protests this summer over the police killings of George Floyd and others — which could’ve had a range of effects, from officers pulling back from their duties to greater community distrust in police, leading to more unchecked violence. Others point to the bad economy. Another potential factor is a huge increase in gun purchases this year. Still others posit boredom and social displacement as a result of physical distancing leading people to cause more trouble.

Above all, though, experts caution it’s simply been a very unusual year with the Covid-19 pandemic. That makes it difficult to say what, exactly, is happening with crime rates. “The current year, 2020, is an extreme deviation from baseline — extreme,” Tracey Meares, founding director at the Justice Collaboratory at Yale Law School, previously told me.

That offers a bit of good news: It’s possible that the end of the pandemic will come and homicide rates will fall again, as they generally have for the past few decades in the US. But no one knows for sure if that will happen, or if we’re now seeing a shift in long-term trends.

Uncertainty about what’s going on isn’t exactly new in the field of criminal justice. Rates of crime and violence have plummeted over the past few decades in the US, yet there is no agreed-upon explanation for why. There are theories applying the best evidence, research, and data available, ranging from changes in policing to a drop in lead exposure to the rise of video games. But there’s no consensus.

That a decades-long phenomenon is still so hard to explain shows the need for humility before jumping to conclusions about the current trends.

“We don’t know nearly enough to know what’s going on at the given moment,” Jennifer Doleac, director of the Justice Tech Lab, previously told me. “The current moment is so unusual for so many different reasons that … it’s really hard to speculate about broad phenomena that are driving these trends when we’re not even sure if there’s a trend yet.”

All of that said, here’s what we do know.

Homicides are up in the US this year

There are several good sources, from criminologists, economists, and other data analysts, for what’s happened with crime and violence so far this year: an analysis by Jeff Asher; a Council on Criminal Justice report written by Richard Rosenfeld and Ernesto Lopez; City Crime Stats, a website from the University of Pennsylvania set up by David Abrams, Priyanka Goonetilleke, Elizabeth Holmdahl, and Kathy Qian; and a preliminary report from the FBI.

Crime analyst Jeff Asher offers the most recent data, looking at crime trends in 51 US cities in 2020 so far compared to 2019. He found murders are up 36 percent. Despite previous comments by President Donald Trump blaming the increase on Democrat-run cities, Asher found murders are up about 36 percent in both cities with Democratic mayors and those with Republican mayors. In a smaller sample of US cities, he found violent crime overall is flat and property crimes are down.

The Council on Criminal Justice report, updated in November, analyzed crime in 28 US cities, ranging in size from Los Angeles to St. Petersburg, Florida, through October. The authors looked for “structural breaks,” in which reported crime increased or decreased more than would be expected, based on data from previous years.

They found structural breaks in homicide, aggravated assault, and gun assault increases, particularly starting in the summer. There weren’t significant increases in domestic assault (although the data for domestic violence is fairly limited), and robbery was actually down. Other kinds of crime, including larceny and drug offenses, largely decreased.

Here’s the graph for homicide increases:

“There were 610 more homicides in the 21 cities in the summer and fall of 2020 than during the same period in 2019,” the report found.

City Crime Stats’ data complicates matters a bit, comparing the 2020 crime trends in 28 major cities to a five-year baseline. With this approach, the homicide increases don’t seem quite as dramatic in many cities, and other types of crime appear to be mostly down as well. Still, homicides do seem to be significantly up in many of the cities included in the City Crime Stats data set.

Here, for example, is Chicago’s homicide trend, which shows this year’s rate (the red line) rising above the five-year baseline (the gray line and shading) at several points throughout the year:

There’s a lot of variation from city to city. Minneapolis, Milwaukee, New York City, and Philadelphia are on the high end of homicides or seeing a flat-out increase. Baltimore, Boston, and Columbus are close to historical trends or actually down.

Overall, though, Abrams said that his data suggests there was a significant increase in homicides from May to June: “We did find a statistically significant increase in homicides — about 21 percent — in aggregate in the cities we looked at in the month after versus before those protests,” he previously told me, cautioning we can’t say with any confidence if the protests were the cause. “Same for shootings, but that’s from a smaller number of cities.”

A preliminary FBI report confirmed these other reports’ findings for the first half of 2020. It found a 15 percent increase in murders, a 5 percent increase in aggravated assaults, and an 8 percent decrease in property crime nationwide from January through June, compared to the same time period in 2019. The FBI will likely release a report for all of 2020 later in 2021.

In Chicago, as well as some other cities, the apparent increase in homicides began before the protests over the police killing of George Floyd. And in some cases, as in Chicago, the spike abruptly ended almost as quickly as it started, only to surge again weeks later, after the protests had calmed. So it’s hard to blame only the protests for a spike — especially because we know that other factors likely played a role, such as the start of summer, when crime tends to go up, and the end of stay-at-home orders.

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City-by-city variation isn’t unique to 2020. It’s expected, even when talking about national crime waves or declines, to see some places go up and others go down for different kinds of crime. The US is a big country, and a range of local factors can affect different kinds of crime.

Still, there’s enough in the four data sets to draw some conclusions: Homicides are up significantly this year. But other kinds of crime, including violent crime overall, aren’t up and may actually have decreased so far this year. There was also a brief spike in burglaries in major cities starting in late May — an increase that was so brief and contained to specific cities that experts told me it was almost certainly due to the riots and looting surrounding some Black Lives Matter protests.

As Asher noted on Twitter, a disconnect between murders and other crimes would be odd: “Violent crime and murder almost always move in the same direction and they are never this far apart nationally.”

One way to reconcile this may be the nature of crime reporting. All of this data is based on reports to governments, typically local police departments. But with people stuck at home, and no government agency operating normally this year, perhaps these reports are just less likely to happen or get picked up, especially lower-level crimes involving drugs or stolen property.

At the same time, it’s far harder for a homicide to go completely unreported — it’s difficult to ignore a dead person. This is why, for much of US history, the homicide rate has been used as a proxy for violent crime overall: The nature of homicide made it a more reliable metric than others for crime.

In other words, it’s possible that other kinds of crime are up this year, but they’re simply going unreported. At any rate, homicides are up significantly.

One note on domestic violence: Some activists and experts worried it would increase this year as people were forced to stay home more often. The Council on Criminal Justice report and City Crime Stats’ analysis suggest that’s not the case, showing no significant change or a drop in some places. But there’s reason for skepticism: Both sources are pulling data from a limited number of cities. And reporting limitations may especially apply to domestic violence, since this year victims are potentially more likely to be trapped with their abusers and unable to make a phone call for help.

There are plenty of caveats to all this data. Much of it only represents trends in large US cities, which means it might not be representative of the country as a whole. And it only covers 2020 through November at the latest.

But the trends, particularly with homicides, are very alarming.

We know less about why there’s a spike, but there are some theories

So why are homicides up?

When I posed this question to experts, they again cautioned that no one can say with certainty what’s going on. That said, they offered some possible explanations, based on the limited information we have so far:

1) The pandemic has really messed things up: Looming over absolutely every discussion about 2020 is the Covid-19 pandemic. That’s no different for discussions about crime and violence. This year is very unusual, with many forced to stay at home and living in fear of a new, deadly virus. That could lead to all sorts of unpredictable behaviors that experts don’t understand yet and might take years to explain.

2) Depolicing led to more violence: In response to the 2014 and 2015 waves of Black Lives Matter protests against police brutality, officers in some cities pulled back, either out of fear that any act of aggressive policing could get them in trouble or in a counterprotest against Black Lives Matter. While protesters have challenged the crime-fighting effectiveness of police, there is a sizable body of evidence that more, and certain kinds of, policing do lead to less crime. Given that, some experts said that depolicing in response to protests could have led to more violence — what some in years past called the “Ferguson effect,” after the 2014 protests in Ferguson, Missouri, over the police shooting of Michael Brown, and also seen in Baltimore after the 2015 killing of Freddie Gray.

3) Lack of trust in police led to more violence: In response to the “Ferguson effect” in 2015, some experts offered a different view of what was happening: Maybe people had lost trust in the police and, as a result, they relied more on street justice and other illegal activities to resolve interpersonal disputes — an interpretation of “legal cynicism,” explained well in Jill Leovy’s Ghettoside and supported by some empirical research. Perhaps Floyd’s killing and the ensuing protests led to a similar phenomenon this year.

4) More guns led to more gun violence: There’s been a big surge in gun buying this year, seemingly in response to concerns about personal safety during a pandemic. And as the research has shown time and time again, more guns mean more gun violence. A recent, preliminary study from researchers at UC Davis already concluded that gun purchases led to more gun violence than there would be otherwise through May this year. That could have further exacerbated homicide increases.

5) Overwhelmed hospitals led to more deaths: One way to explain a flat or dropping violent crime rate as homicides rise is that the violent crime was deadlier than usual. With health care systems across the US at times close to capacity or at capacity due to Covid-19, maybe hospitals and their staff couldn’t treat violent crime victims as well — increasing the chances they died this year. That could translate to more deaths, and homicides, even if violent crime remained flat or declined.

6) Idle hands led to more violence: Throughout the pandemic, a lot of people have been bored — with forms of entertainment, from restaurants to movie theaters, closed down. Schools are limited or closed too, and millions have been newly unemployed. Other support programs that can prevent violence were shuttered due to the closures. All of that could have led to conflict, and possibly more crime and violence. But, experts cautioned, this is speculative, with little evidence so far to support it.

7) A bad economy led to more violence: With the economy tanking this year, some people may have been pushed to desperate acts to make ends meet. Disruptions in the drug market, as product and customers dried up in a bad economy, may have led to more violent competition over what’s left. The bad economy also left local and state governments with less funding for social supports that can keep people out of trouble. All of that, and more, could have contributed to more crime and violence — but this, too, is still very speculative.

Another possibility: None of these explanations is right. With limited data in strange times, it wouldn’t be surprising if it turns out we have no idea what’s going on right now. “We can bet on it being unpredictable,” Doleac said.

Again, there’s still no consensus about what’s caused crime to decline since the 1990s. In that context, it’s no surprise there’s nowhere near a consensus as to why a homicide spike has occurred so far this year.

The trends could change after a strange 2020

It’s possible that before we understand why it’s happening, the year’s alarming homicide trends could recede. It’s happened before: In 2005 and 2006, the homicide rate briefly increased, only to start declining again before hitting record lows in 2014. In 2015 and 2016, the rates also spiked again only to start to dip after. In both instances, these years were effectively blips and the overall crime decline America has seen for the past three decades continued.

Maybe after this very weird year ends, crime and violence trends will, similarly, go back to the previous normal.

But that’s not a guarantee — and it’s not something we should rely on, experts said. “We don’t really understand why crime and violence went down,” John Roman, a criminal justice expert at NORC at the University of Chicago, previously told me. “Being able to say we should expect this unexplained phenomenon to continue strikes me as sort of irrational.”

Even if we can’t explain what may be causing a homicide spike, there are certain strategies that might help fight crime in the short term — such as deploying police in crime hot spots (though that would have to be done carefully and with reforms, given the current political climate around policing), a “focused deterrence” program that targets the few people in a community engaging in violence with a mix of support and sanctions, and using civilian “interrupters” to personally intervene in cases in which violence seems likely to break out.

Notably, a lot of this work is done at the local and state level, where the vast majority of police departments are based. The federal government can incentivize certain practices, like President-elect Joe Biden has proposed doing, but it ultimately falls on cities, counties, and states to carry out new or revised approaches.

Many of the evidence-based approaches rely on in-person contact, which requires ending the pandemic. “The police, public health, and community approaches to violence reduction require that people meet face-to-face; they cannot be replaced by Zoom,” Rosenfeld and Lopez wrote in one of their reports. “An underappreciated consequence of the pandemic is how social-distancing requirements have affected outreach to high-risk individuals.”

So the first priority should be to end the pandemic — ending its potential ripple effects on crime and enabling evidence-based approaches that can help reduce crime. But to do that, the US public and governments will need to truly embrace strategies that have worked for countries like South Korea and Germany against Covid-19: physical distancing, masking, and testing, tracing, and isolating the sick. In this sense, Trump’s failures to address Covid-19 may be leading to more violence.

“Seeing what’s happening with these [crime] numbers can point us to or at least get us thinking about what potential policy levers we could employ that would be helpful,” Doleac said. “Otherwise, our attention is probably better focused on making sure we’re all wearing masks.”

Beyond the pandemic, police are going to have more trouble fighting crime — including any current or future spikes — if large segments of the community don’t trust them. That’s where police reform comes into play. It’s a complicated topic, separate from a possible spike in violence this year. But, in short, experts say police should, at a minimum, show the communities they serve that they understand the concerns, acknowledge mistakes, and will change how officers are trained and deployed.

Otherwise, there’s a good chance that protests against police will flare up, just as they did from 2014 to 2016 and have again this year. If protests lead to more violence — whether by leading to depolicing, or sowing and exposing distrust in law enforcement — that’s going to create public safety problems.

To put it another way: There’s a lot we don’t know about crime, why it happens, and how to stop it. But it’s going to be much easier to wrap our heads around these issues once things get closer to how they should be — and that means seriously addressing the pandemic and protests against police brutality.

Unfortunately, the US is going in the opposite direction, with a surge of Covid-19 this fall and winter and Trump exacerbating police-community tensions with his rhetoric and push to deploy unsolicited federal agents in some US cities.

“How optimistic should we be for the rest of the summer?” Roman said. “I think the answer is not terribly optimistic, because none of these factors seem to be abating with the return of Covid.”

If someone told you in March, when the World Health Organization finally called the Covid-19 outbreak a pandemic, that we’d have three strong coronavirus vaccine candidates by mid-November, you might have called that person delusional.

Yet with Monday’s news from AstraZeneca and University of Oxford that early results from their phase 3 trial demonstrate their vaccine’s effectiveness, that’s exactly the scenario we’re in.

In a press release, the pharmaceutical giant and its Oxford co-developers reported interim findings from two groups in their ongoing trials — one in the UK and one in Brazil. The trials used different approaches to inoculating the people who participated, and found two levels of efficacy, which they averaged to 70 percent. The researchers also found no severe cases or hospitalizations in the study participants who got the vaccine.

In the UK trial group AztraZeneca reported on, the vaccine — known as AZD1222 — was given as a half dose, followed by a full dose around one month later, resulting in 90 percent efficacy. In the Brazil group, study participants were given two full doses at least one month apart, and the efficacy was 62 percent.

The researchers aren’t sure why there was this striking gap in vaccine performance — and in a press conference, said that the half dose may better prime the immune system to respond to the second full vaccine. But while the company framed the reason for the half dose was “serendipity” — in reality, the trial participants were given a smaller dose in error. And while it appears the accidental dosing regimen may have outperformed two full doses, independent researchers wondered about whether it was administered to enough people to know for sure. (More on that in a moment.)

Either way, 50 percent efficacy is the floor set by the US Food and Drug Administration and the European Medicines Agency (the FDA equivalent in Europe) for approval. The AstraZeneca-Oxford research team will “immediately” submit their findings to regulatory agencies around the world, seeking early approval.

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While the efficacy outcome falls short of the 95 percent preliminary result recently reported by both Moderna and Pfizer/BioNTech, the results, if real, could be promising. At around $3 to $4 per dose, the AstraZeneca-Oxford shot is the cheapest of the three current options and should be easier to distribute globally (since it can be stored in regular refrigerators). That’s why lower-income countries around the world have been pre-purchasing access.

But, as with all the new coronavirus vaccine candidates, there are some big caveats to consider. And since the results came via press release and lacked detailed data, they raise questions we don’t yet have answers to. Here’s the rundown.

The Oxford-AstraZeneca vaccine could be a game changer for low- and middle-income countries

Among the Covid-19 vaccines furthest along in development, the AstraZeneca-Oxford candidate is among the most likely to be affordable to low- and middle-income countries. And considering much of the world’s population currently lives in low- and middle-income settings, it’s the jab that — with a 90 percent efficacy result — could make a big dent in the pandemic worldwide.

It also uses a novel approach to inoculation, one that’s different from Pfizer-BioNTech and Moderna — and from conventional vaccines.

Vaccine makers have typically used the virus itself or a fragment of the virus, often in a weakened or inactivated form, to inoculate recipients. But this new generation of vaccines uses genetic instructions for making parts of the SARS-CoV-2 virus that causes Covid-19. All three candidates — Pfizer, Moderna, and AstraZeneca-Oxford — deliver the instructions for making the SARS-CoV-2 spike protein, or the part of the virus that lets it enter human cells. And it’s these instructions, which human cells then use to manufacture parts of the virus, that are injected into vaccine recipients, essentially coaching the immune system to fight off the invader should it arrive.

The Moderna and Pfizer-BioNTech vaccines both use mRNA as their platform for delivering the genetic instructions. AstraZeneca-Oxford’s uses DNA instead, and the DNA is delivered to cells with the help of another virus known as an adenovirus. (Other Covid-19 vaccine developers, like CanSino Biologics and Johnson & Johnson, are also using adenovirus vectors.)

AstraZeneca, unlike Moderna and Pfizer/BioNTech, has promised to sell its shot at cost — around $3 to $4 — and not to profit from the vaccine while the pandemic is ongoing (though public money has gone into funding its research effort). According to the FT, that price is “a fraction” of the expense of the other vaccine candidates, which are expected to cost between $15 and $25 per dose.

Also unlike the two other leading vaccine candidates, it doesn’t require extremely cold temperatures for storage. That’s the distribution hurdle Moderna and Pfizer-BioNTech are working to overcome.

Moderna’s vaccine requires long-term storage at minus 20 degrees Celsius (minus 4 degrees Fahrenheit) and is stable for 30 days at refrigerator temperatures between 2 and 8 degrees Celsius (36 to 46 degrees Fahrenheit). Meanwhile, the Pfizer-BioNTech vaccine demands ultra-cold temperatures of minus 70 degrees Celsius (minus 94 degrees Fahrenheit) or lower, with about five days of shelf life at refrigerator temperatures. The AstraZeneca-Oxford vaccine can be stored in a normal refrigerator for at least six months.

So these are the reasons why the AstraZeneca-Oxford vaccine has become a leading contender lower-income countries are relying on to end their epidemics. For now, the shot “accounts for more than 40% of the supplies” going to low- and middle-income countries, according to Bloomberg. AstraZeneca said the company has the capacity to supply 3 billion doses of the vaccine in 2021.

“[T]he vaccine’s simple supply chain and our no-profit pledge and commitment to broad, equitable and timely access means it will be affordable and globally available supplying hundreds of millions of doses on approval,” said Pascal Soriot, CEO of AstraZeneca, in a statement.

The US is also poised to benefit. In May, the Biomedical Advanced Research and Development Authority (BARDA) under the Department of Health and Human Services pledged up to $1.2 billion to back the AstraZeneca-Oxford vaccine, aiming to secure 300 million doses for Americans.

Of course, if the shot only has around 70 percent efficacy, officials will have to grapple with how and where it’s used at all. “If it’s 70%, then we’ve got a dilemma,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told Stat. “Because what are you going to do with the 70% when you’ve got two [vaccines] that are 95%? Who are you going to give a vaccine like that to?”

The caveats

That’s not the only caveat to consider. The AstraZeneca-Oxford results so far came via press release, and gloss over nuances we’d need to understand to know how the vaccine works in people. AstraZeneca-Oxford also released fewer details about their research than the other two companies, and reported their results in a way that made drawing comparisons among the three candidates difficult. Let’s go over what we know.

• Before clinical trials begin, research groups are supposed to publicly share a plan — called a protocol — for how they’ll run the studies and analyze and share the results, and they’re supposed to stick to it. That helps ensure experimenters don’t move the goalposts to come to more favorable conclusions.

But AztraZeneca and Oxford have only shared two of the protocols for their phase 3 studies after the trials began. We have the protocol for their US phase 3 study, and as writer and meta-scientist Hilda Bastian points out in Wired, a UK protocol published in a Lancet study appendix, also shared after the trial started.

“The appendix doesn’t say when this became the plan. We don’t even know if the Oxford-AstraZeneca team followed it,” Bastian writes. Again, in the press release, AstraZeneca also only disclosed data for subgroups in two of the trials, not the four specified in the UK protocol, she told Vox. “We do know [what’s in the protocol] is not what they reported.” “Transparency can increase confidence in the trials and are essential for establishing the quality of the science. [Six companies or research groups] have released protocols for their phase 3 studies — why not Oxford?” asked Peter Doshi, who has been a prominent critic of Covid-19 vaccine trials.

• The press release doesn’t report details of what side effects the study participants experienced. The company only reported there were no serious safety events confirmed to date, and that the vaccine “was well tolerated across both dosing regimens.” We do know that the UK trial for AZD1222 was paused in July and again in September after two volunteers reported neurological problems. Investigations later found no link between the vaccine and these symptoms, and regulators allowed the trial to resume in October.
• While we know the number of participants included in each in the UK and Brazil trials (2,741 in the UK versus 8,895 in Brazil), we don’t know how many got the vaccine (versus a placebo or meningococcal vaccine), which raised a statistical question about how many people were infected with the virus in the UK group that saw 90 percent efficacy. Some statisticians have suggested the number may be very small — and potentially unreliable:

• The press releases also lack details about the demographics of people participating in the trials. AstraZeneca said its trial participants come from “diverse racial and geographic groups who are healthy or have stable underlying medical conditions,” but without knowing the exact numbers, it’s hard to gauge how well they reflected the groups most at risk of severe disease (including older adults and people of color).
• The trials also didn’t use a simple placebo to measure efficacy. In the UK arm of the trial, volunteers were randomly assigned to receive the AZD1222 vaccine or the meningococcal vaccine. In the Brazil arm, the comparison group was given the meningococcal for the first dose and a saline placebo for the second dose.
• Another factor to consider: AstraZeneca-Oxford measured their results in a different way from their two major competitors. The Moderna and Pfizer/BioNTech trials only captured Covid-19 infections in their trial pool that advanced far enough to produce symptoms, while the AstraZeneca trials conducted weekly swab tests among their participants, allowing them to detect much less severe cases — including potential asymptomatic infections — among their volunteers. These differences make it trickier to draw apples-to-apples comparisons of the efficacy of the different vaccines.

Together, these factors highlight that there’s still a lot to learn about the new vaccines, even as they’re all set to roll out imminently. The Moderna, Pfizer-BioNTech, and Oxford-AstraZeneca teams have all vowed to publish their trial results in peer-reviewed journals. But distribution on a limited emergency use basis may begin as soon as next month, pending approval from regulators.

For now, it’s worth pausing over how remarkable it is that there are several SARS-CoV-2 vaccine candidates that have reported high levels of efficacy, featuring technologies that have never been deployed at a large scale in humans before.

If the AstraZeneca-Oxford, Moderna, and Pfizer-BioNTech groups pass regulators, the coronavirus vaccines may be the beginning of an entirely new approach to inoculating people against disease.

Clarification, December 4: An earlier version of this story stated that AstraZeneca/Oxford only shared the protocol for their US study. While that was the only phase 3 protocol registered on their clinical trials database, the researchers also shared the protocol for the UK trial in an appendix in a journal article.

MAYO HAVE MADE five changes for Saturday night’s trip to Omagh for a repeat of last year’s All-Ireland final against Tyrone.

David McBrien comes in at full-back for his first league start of the season, with Castlebar Mitchels youngster Donnacha McHugh named to start alongside him. Fionn McDonagh, Jason Doherty and Paul Towey are the three players drafted into attack.

Padraig O’Hora, Michael Plunkett, Jack Carney, Diarmuid O’Connor and Paddy Durcan are the players to make way. There are several positional changes, most notably in Aiden O’Shea named at centre-back.

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Throw-in is 5.45pm at Healy Park as Mayo seek to rebound from last Saturday’s loss to Kerry while Tyrone look to recover from Sunday’s defeat to Dublin.

Mayo

1. Rob Hennelly (Breaffy)

2. Lee Keegan (Westport), 3. David McBrien (Ballaghaderreen), 4. Donnacha McHugh (Castlebar Mitchels)

5. Oisín Mullin (Kilmaine), 6. Aidan O’Shea (Breaffy), 7. Stephen Coen (Hollymount-Carramore, captain)

8. Jordan Flynn (Crossmolina Deel Rovers), 9. Matthew Ruane (Breaffy),

10. Fionn McDonagh (Westport), 11. Paul Towey (Charlestown), 12. Fergal Boland (Aghamore)

13. Aiden Orme (Knockmore), 14. Jason Doherty (Burrishoole), 15. Ryan O’Donoghue (Belmullet)

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On Wednesday, under increasing criticism for the state’s slow vaccine rollout, Gov. Gavin Newsom (D) announced that all Californians 65 and older will be eligible for the shot.

But if you were a Californian who wanted to find more information about where to get that shot for yourself or your loved one, you would’ve been out of luck. While the state’s website has been updated to say that individuals 65 or older are eligible, there are no tools to find a nearby location where vaccines are available. The state’s official FAQ answers the question, “How can I get the Covid-19 vaccine?” with, “Most Californians will be vaccinated at community vaccination sites, doctor’s offices, clinics, or pharmacies” — no links, no instructions about how to find one near you.

So, fed-up Californians are taking matters into their own hands: they’re crowdsourcing it. In the last two days, an effort has sprung up to report on where shots are available to the elderly. Volunteers have set up a spreadsheet with a simple premise: One person can call each location every day and ask if vaccines are available, and then publish the information for everyone to see. (There’s a way to submit updates and corrections, too.) Once the team is confident in their two-day-old system, they’ll open up crowdsourcing and reporting, soliciting more help and more publicity so it can reach more Californians.

The crowdsourced list of where Covid-19 vaccines are available, and to whom, is a microcosm of both everything good and everything utterly broken about the United States’ coronavirus response.

Throughout the pandemic, national coordination has been lacking, causing public health tasks to fall to states and counties that vary dramatically in their preparedness to take them on. Coordination tasks that should be the business of government — from ensuring that there’s enough personal protective equipment (PPE) for hospital workers to reporting data on Covid-19 cases to letting people know which clinics offer vaccines — have fallen to hospitals themselves, or even to individuals.

Against that grim backdrop, people have stepped up, over and over, to get things done where our institutions have failed. In Washington State, university researchers studying the flu were among the first to detect the novel coronavirus in the country, while the CDC floundered. In Florida, a lone fired data scientist kept the state’s citizens updated about coronavirus case numbers. Journalists and researchers like Zeynep Tufekci told the public to wear masks and to worry about ventilation long before official organizations like the CDC and WHO recommended that. A group of citizens developed and published a risk points calculator to help people understand the risks of different daily activities.

And now in California, volunteers are trying to figure out which hospitals have enough vaccine supply to vaccinate elderly Americans. Should such a task fall to them? No. But since it has, I’m glad we have them.

How California got an unofficial vaccine availability dashboard overnight

Few US states have done an impressive job of rolling out the desperately needed Covid-19 vaccines in the month since the FDA approved them, but the most populous state, California, is among those having a particularly poor showing. The state with the best vaccination program, West Virginia, has used 78.6 percent of the doses shipped to it; California has used 27 percent, putting it 49th in the country. (Only Alabama, at 21 percent, is doing worse.) Seven percent of West Virginians have been vaccinated; only 2.5 percent of Californians have.

On Wednesday, January 13, Newsom announced that people aged 65 and older could be vaccinated in California, as part of a push to improve the state’s dismal overall vaccination performance. (Newsom’s office has not responded to a request for comment.) Yet California is lacking the infrastructure for vaccine availability reporting that many other states have, though some counties have their own systems. For instance, West Virginia’s vaccination website lists every clinic conducting vaccinations each day, with an address and specific details about how to get a vaccine. Texas has a huge map of vaccination locations across the whole state, with the ones with availability highlighted.

The unofficial California dashboard came together as a result of a call to arms on Twitter from Patrick McKenzie, a well-known tech worker and writer currently at Stripe, a payments company that before the pandemic was based in San Francisco.

McKenzie went on to clarify that he and others would reimburse anyone who spent their own money out of pocket on setting up a system. Californians immediately chimed in with their stories of frustration at trying to get a vaccine:

Having every person in California who needs a vaccine call every doctor’s office until they find one that has availability is, obviously, a terrible way to distribute vaccines; doctors’ offices will be swamped with calls, while at-risk Americans may become dispirited and give up on getting the shot.

So more than 70 volunteers got to work. Ideally, every clinic would get only one call, every day, asking about availability that day; then the information would be made public so eligible residents could figure out where they could get the vaccine without having to make the calls themselves. A Google spreadsheet was linked, then migrated to an AirTable (a spreadsheet/database service with more flexibility than Google Sheets offers). A list of clinics and hospitals and contact information was compiled, and the team got to work calling them.

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The reports started flowing in, each one a window into a chaotic vaccination system. “Only doing 75 and older right now, and asked me to call the county public health department at 408 792 5040 to schedule an appointment. That number redirects to 211 at the moment for Coronavirus related concerns and reached a full voicemail box otherwise,” the notes for one report for a hospital read.

Another reads, “says that Yolo county hasn’t had any direction [to start vaccinating elderly Californians], still on [Phase] 1A only.”

“We’re not offering that in LA County yet. I know Orange County’s offering it, but you have to be an Orange County resident,” another caller was told.

There was some good news too. As of January 14, Kaiser, the Oakland-based health care system, has availability for Kaiser patients 65 and older. Sutter Health, another California-based health care system, has availability for Sutter Health patients 75 and older. Ralph’s, the Southern California grocery store, has some slots.

And the site has already been used to get some people vaccinated:

But overall, Newsom’s Wednesday declaration that people 65 and older are eligible to be vaccinated hasn’t translated to policy changes at the vast majority of hospitals in California. Whatever has California so far behind West Virginia, it will take more than an expansion of eligibility — or a crowdsourced tool — to fix.

State and local governments have been put to an extraordinary test over the last year. Many California county health departments have been models of how to handle the pandemic, from their early action declaring an emergency in March to the low death counts all year.

But the vaccination rollout has made it clear that good local governance can’t solve everything. Without good statewide coordination and communication, and without funding, counties simply can’t help everyone eligible for a vaccine arrange to get one. Good county governments and individual/crowdsourced efforts can take over many key government functions, but without state and federal coordination, vaccine distribution will be more chaotic than it should be.

In light of that, perhaps the biggest benefit from a tracking project like this one is accountability. Calling up clinics across California systematically makes it clear that many counties and many hospitals aren’t vaccinating people aged 65 and older, whatever Newsom says. In some areas, clinics are still vaccinating their own health care workers, even though many other states finished vaccinating all willing front-line health care workers earlier this month and moved on to other priority groups.

It makes it clear that many of the state’s most vulnerable citizens are getting shuffled between websites and phone lines, often with no vaccine at the end of the journey — and it cuts through that confusion and mess to find the locations that are getting shots into elderly residents’ arms.

Eventually, maybe Californians will get answers about why the vaccine rollout was botched so badly. In the meantime, though, the answer that can’t wait — which clinics are open — is available online.

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DeepMind, an AI research lab that was bought by Google and is now an independent part of Google’s parent company Alphabet, announced a major breakthrough this week that one evolutionary biologist called “a game changer.”

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“This will change medicine,” the biologist, Andrei Lupas, told Nature. “It will change research. It will change bioengineering. It will change everything.”

The breakthrough: DeepMind says its AI system, AlphaFold, has solved the “protein folding problem” — a grand challenge of biology that has vexed scientists for 50 years.

Proteins are the basic machines that get work done in your cells. They start out as strings of amino acids (imagine the beads on a necklace) but they soon fold up into a unique three-dimensional shape (imagine scrunching up the beaded necklace in your hand).

That 3D shape is crucial because it determines how the protein works. If you’re a scientist developing a new drug, you want to know the protein’s shape because that will help you come up with a molecule that can bind to it, fitting into it to alter its behavior. The trouble is, predicting which shape a protein will take is incredibly hard.

Every two years, researchers who work on this problem try to prove how good their predictive powers are by submitting a prediction about the shapes that certain proteins will take. Their entries are judged at the Critical Assessment of Structure Prediction (CASP) conference, which is basically a fancy science contest for grown-ups.

By 2018, DeepMind’s AI was already outperforming everyone at CASP, provoking some melancholic feelings among the human researchers. DeepMind took home the win that year, but it still hadn’t solved the protein folding problem. Not even close.

This year, though, its AlphaFold system was able to predict — with impressive speed and accuracy — what shapes given strings of amino acids would fold up into. The AI is not perfect, but it’s pretty great: When it makes mistakes, it’s generally only off by the width of an atom. That’s comparable to the mistakes you get when you do physical experiments in a lab, except that those experiments are much slower and much more expensive.

“This is a big deal,” John Moult, who co-founded and oversees CASP, told Nature. “In some sense the problem is solved.”

Why this is a big deal for biology

The AlphaFold technology still needs to be refined, but assuming the researchers can pull that off, this breakthrough will likely speed up and improve our ability to develop new drugs.

Let’s start with the speed. To get a sense of how much AlphaFold can accelerate scientists’ work, consider the experience of Andrei Lupas, an evolutionary biologist at the Max Planck Institute in Germany. He spent a decade — a decade! — trying to figure out the shape of one protein. But no matter what he tried in the lab, the answer eluded him. Then he tried out AlphaFold and he had the answer in half an hour.

AlphaFold has implications for everything from Alzheimer’s disease to future pandemics. It can help us understand diseases, since many (like Alzheimer’s) are caused by misfolded proteins. It can help us find new treatments, and also help us quickly determine which existing drugs can be usefully applied to, for example, a new virus. When another pandemic comes along, it could be very helpful to have a system like AlphaFold in our back pocket.

“We could start screening every compound that is licensed for use in humans,” Lupas told the New York Times. “We could face the next pandemic with the drugs we already have.”

But for this to be possible, DeepMind would have to share its technology with scientists. The lab says it’s exploring ways to do that.

Why this is a big deal for artificial intelligence

Over the past few years, DeepMind has made a name for itself by playing games. It has built AI systems that crushed pro gamers at strategy games like StarCraft and Go. Much like the chess matches between IBM’s Deep Blue and Garry Kasparov, these matches mostly served to prove that DeepMind can make an AI that surpasses human abilities.

Now, DeepMind is proving that it has grown up. It has graduated from playing video games to addressing scientific problems with real-world significance — problems that can be life-or-death.

The protein folding problem was a perfect thing to tackle. DeepMind is a world leader in building neural networks, a type of artificial intelligence loosely inspired by the neurons in a human brain. The beauty of this type of AI is that it doesn’t require you to preprogram it with a lot of rules. Just feed a neural network enough examples of something, and it can learn to detect patterns in the data, then draw inferences based on that.

So, for example, you can present it with many thousands of strings of amino acids and show it what shape they folded into. Gradually, it detects patterns in the way given strings tend to shape up — patterns that human experts may not have detected. From there, it can make predictions about how other strings will fold.

This is exactly the sort of problem at which neural networks excel, and DeepMind recognized that, marrying the right type of AI to the right type of puzzle. (It also integrated some more complex knowledge — about physics and evolutionarily related amino acid sequences, for example — though the details remain scant as DeepMind is still preparing a peer-reviewed paper for publication.)

Other labs have already harnessed the power of neural networks to make breakthroughs in biology. At the beginning of this year, AI researchers trained a neural network by feeding it data on 2,335 molecules known to have antibacterial properties. Then they used it to predict which other molecules — out of 107 million possibilities — would also have these properties. In this way, they managed to identify brand-new types of antibiotics.

DeepMind researchers are capping the year with another achievement that shows just how much AI has matured. It’s genuinely great news for a generally terrible 2020.

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President-elect Joe Biden announced a plan on Friday for what will likely be his most pressing challenge when he takes the White House next week: fixing America’s messy Covid-19 vaccine rollout.

The plan builds on Biden’s $1.9 trillion economic stimulus proposal, which included a $400 billion Covid-19 plan, announced on Thursday. It seeks more support to states and lower levels of government, a greater expansion of vaccine eligibility, funding for more public health workers, a boost in vaccine production, better communication about the vaccines, an education and awareness campaign, and more. He promises 100 million vaccine doses delivered in his first 100 days in office.

Above all, the plan aims for something that President Donald Trump’s administration didn’t do with Covid-19 more broadly and the vaccine in particular: greater federal involvement. The Trump administration has repeatedly pushed against a bigger federal role — even characterizing more support for states so they can get shots in arms as a “federal invasion.” Biden has rejected that rhetoric, calling for a bigger role by the feds, and cementing it with his plan.

The stakes are as high as they’ve ever been. The country now averages 240,000 Covid-19 cases and more than 3,300 deaths each day. The American death toll is among the worst in the world, with the country now approaching a total of 400,000 dead. If the US had the same death rate per million people as Canada, over 230,000 more Americans would likely be alive today.

The vaccine is America’s — and the world’s — chance at fixing this mess. Experts say the country must vaccinate at least 70 percent of its population, and possibly more, to reach herd immunity and protect a sufficient amount of the population from the virus. Only then can outbreaks truly be curbed.

But the US has been slow in rolling out a vaccine. The Trump administration overpromised and underdelivered: It promised 40 million doses and 20 million people vaccinated by the end of 2020; two weeks into 2021, only 31 million does have been delivered and just 11 million Americans have received at least the first dose of a vaccine, according to federal data. The country is currently not on track to reach 70-plus percent vaccination rates by the end of the summer.

Biden’s immediate challenge is to clean this all up. His presidency may count on it — his handling of the country’s most pressing crisis will likely be what Americans judge him on over the next year.

More seriously, it’s a matter of life or death: With thousands of people dying each day, ending the epidemic in the US even days or weeks earlier than otherwise could save up to tens or hundreds of thousands of lives.

Here’s how Biden plans to do it.

What Biden’s vaccine plan does

Biden promises to leverage “the full strength of the federal government,” in partnership with state, local, and private organizations, for a truly national vaccine plan. You can read the full proposal here, but these are some of the key points:

• More federal work to get shots to people: Biden calls for more involvement by the federal government in getting vaccine doses to people. That includes new vaccination centers, mobile vaccination units in underserved communities, reimbursement of states’ National Guard deployments, and expanding vaccine availability in pharmacies. He also promises to target hard-to-reach, marginalized communities with extra support, particularly those that have been hit the hardest by Covid-19.
• Boost the supply of vaccines: Biden says he’ll make greater use of federal powers, such as the Defense Production Act, to boost the manufacture of vaccines and related supplies. He also says he’ll improve communication with states so they can better understand when and how much vaccine they can expect to get — addressing a big complaint from states today, as the Trump administration has often failed to inform them of even these basic details.
• Expanded vaccine eligibility: Biden calls for expanding vaccine eligibility to include everyone 65 and older as well as frontline essential workers, including teachers, first responders, and grocery store employees. Several states have already moved in this direction, but Biden promises more support and encouragement toward this objective.
• Mobilize a larger public health workforce: Building on his stimulus plan, Biden vows to hire and use a larger public health workforce to help deploy the vaccine across the country. He’ll also take other steps, like allowing retired medical professions who aren’t currently licensed under state law to help administer vaccines “with appropriate training.”
• Launch a national public education campaign: To help convince people to get vaccinated, Biden also plans to launch an education campaign “that addresses vaccine hesitancy and is tailored to meet the needs of local communities.”

All of that is on top of Biden’s broader Covid-19 plan, which promises $400 billion more funds to combat the coronavirus and, specifically, $20 billion more for vaccine efforts.

Biden’s plan hits many of the marks that I’ve heard from experts over the past few weeks as I’ve asked them about what’s going wrong with America’s vaccine rollout.

First, the plan has clear goals to address what supply chain experts call the “last mile” — the path vaccines take from storage to injection in patients — by making sure there’s enough staff, infrastructure, and planning to actually put shots in arms. Second, it takes steps to ensure that supply chain problems are fixed proactively, with careful monitoring and use of federal powers when needed to address bottlenecks. Last, but just as crucially, there’s a public education campaign to ensure that Americans actually want to get vaccinated when it’s their turn.

The question, of course, is if all of this can get implemented properly. As the US response to Covid-19 has floundered, a key question has been how much of the failure is attributable just to Trump versus bigger systemic problems, like the country’s size and sprawl, fractured health care system, and fragmented federalist government.

There’s also the question of whether Biden can get the congressional support needed for all these efforts. Democrats will control both houses of Congress. But more moderate wings of the party may scoff at the high price tag: Biden’s stimulus plan is estimated at $1.9 trillion and the Covid-19 plan alone (which is included in the bigger plan) at $400 billion. The cost of borrowing money is low, and Biden argues that the risk right now is doing too little instead of too much, but it remains to be seen if he gets enough backing in Congress.

If he pulls it off, though, Biden has a chance to show how much of a difference true federal leadership can make — and demonstrate how much the previous administration failed by refusing to embrace a larger role for itself.

Biden wants a federal role that Trump disavowed

At the core of Biden’s plan is a posture of more federal involvement that Trump has resisted at every step throughout the Covid-19 crisis.

This was clear in Biden’s broader Covid-19 plan, too: The ideas in the proposal aren’t at all new. Experts have called for expanding testing, preparing for mass vaccination efforts, supporting schools, providing emergency paid leave, and much more in the past year. Biden himself proposed many of these things last March. You can see many of these ideas in article after article in Vox and elsewhere, dating back to early 2020.

The Trump administration declined more aggressive steps, repeatedly taking a stance that it wasn’t the federal government’s proper role to get hands-on with the Covid-19 response. With protective equipment, Trump resisted using the Defense Production Act to get more masks, gloves, and other gear to health care workers. On testing, the Trump administration left the bulk of the task to local, state, and private actors, describing the federal government as merely a “supplier of last resort.” On tracing, the administration never had anything resembling a plan to make sure the country could track down the sick or exposed and help them isolate or quarantine.

This kind of hands-off, leave-it-to-the-states attitude culminated in the messy vaccine rollout. While there are many factors contributing to America’s slow vaccine efforts — including the country’s size, sprawl, and fragmented health care system — a key contributor is the lack of federal involvement. In effect, the Trump administration purchased tens of millions of doses of the vaccines, shipped them to the states, and then left the states to figure out the rest.

This was clear in the funding numbers. State organizations asked for $8 billion to build up vaccine infrastructure. The Trump administration provided $340 million. Only in December did Congress finally approve $8 billion for vaccine distribution, but experts say that money comes late, given that vaccination efforts are already well underway and the funds could’ve helped in the preparation stages.

When asked about the botched vaccine rollout, the Trump administration has stuck to its anti-federalist stance — arguing that it’s on states and localities to figure out how they can vaccinate more people. Brett Giroir, an administration leader on Covid-19 efforts, argued, “The federal government doesn’t invade Texas or Montana and provide shots to people.”

Characterizing greater federal support for Covid-19 efforts as a federal invasion is of course absurd, but it’s emblematic of the Trump administration’s approach to the crisis.

On vaccines, as with the coronavirus in general, Biden’s promise has long been that he’ll embrace a bigger role for the federal government. With his plan, Biden is putting some specific details to that end. The question now is if he can pull it off — if he gets the support he needs from Congress, and if the feds really can deliver what Biden has promised.

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There’s a reason why a new, more contagious variant of SARS-CoV-2 appeared first in the UK: The country does a lot of viral genetic sequencing. Since the start of the pandemic, researchers in the UK have uploaded 151,859 individual SARS-CoV-2 sequences to GISAID, an international platform for sharing viral genomic data. That’s the highest number of sequences shared by any country in the world.

If a more contagious strain of SARS-CoV-2 first evolved in the United States, scientists likely would not have noticed so quickly. Despite having a larger population than the UK, a sophisticated biomedical research industry, and tens of millions more cases of Covid-19, to date US labs have only uploaded 69,111 sequences, according to GISAID.

“It’s embarrassing, is all I can say,” Diane Griffin, a microbiologist and immunologist at Johns Hopkins, told Vox.

The US has lagged behind on so many aspects of pandemic response — from an initial lack of testing, to the current strained and clumsy rollout of the Covid-19 vaccines. Lack of genetic surveillance is just another. Without it, we’re kept in the dark: Scientists can’t see, clearly or quickly, how and if the virus is mutating in concerning ways. It also leaves us without another useful tool to deploy in contact tracing studies.

And it’s one this country ought to invest in, and get right, scientists say — at least before the next pandemic strikes.

How the US fails on testing viral genomes

Earlier this year, Griffin was on a committee making recommendations for a recent National Academies of Science report on the state of genomic surveillance in the US. Genomic surveillance is used, routinely, around the world to track flu, and to try to predict which flu vaccine strains will be most effective in a given season. Genetic sequencing tools are not a new technology, and the Academies wanted a report to survey how they were being deployed in the pandemic in the US. Genetic sequencing is of particular import when it comes to coronaviruses because they use RNA as their genetic code, and RNA viruses are known to mutate frequently.

The report, when it was published in July, outlined a bleak landscape of SARS-CoV-2 mutation tracking. It’s not just that the US isn’t collecting enough genome samples of the virus. It’s doing so in an unsystematic, patchwork way.

“Current sources of SARS-CoV-2 genome sequence data … are patchy, typically passive, reactive, uncoordinated, and underfunded in the United States,” the report concluded. And the data that did exist? The report found it was “inadequate to answer many of the pressing questions about the evolution and transmission of the virus.”

Early on in the pandemic — way back in March — the UK government invested £20 million ($27 million) to launch the COVID-19 Genomics UK (COG-UK) consortium, which coordinates the collection of this data from public health labs. The consortium also tracks viral genetic samples from health clinics, university research labs, and public health research facilities, to help generate a close-to-real-time snapshot of how the virus is changing in the country.

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It’s what allows researchers to generate maps like this one, which shows how the new, more contagious strain of the virus spread geographically in the country over time.

The rich genetic data, when paired with case reports, also guides researchers to ask and answer crucial questions, such as: Is this new variant more deadly than other ones? Scientists were able to quickly determine the answer is “no.” (That said, a more contagious virus can still end up killing more people than a more virulent one.)

The US Centers for Disease Control and Prevention does have a genetic surveillance program called SPHERES (SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance), but it’s less well coordinated than the UK effort. Right now labs have to essentially raise their hands and volunteer to contribute. And the funding for their efforts isn’t consistent. That leads to a patchwork of surveillance across the country. “So you might know what’s going on in Boston, or New York City, but have no idea what’s going on in Iowa,” Griffin says.

“In other words,” says Stanford microbiologist David Relman, who also contributed to the National Academies report, “anybody who has the means and interest to engage in genomics is certainly encouraged to do so.” But genomic sequencing, he says, hasn’t been made a “mainstream central pillar of public health efforts.”

What we lose out on when we don’t collect genetic samples of circulating viruses

The National Academies report was published in July. Has the situation gotten much better since? “No,” Griffin says. There has been a little bit of positive movement: Recently, private genomics companies Illumina and Helix have started to help in the detection of new variants in the United States. Even so, James Lu, president of Helix, told MIT Technology Review the US still needs to go from sequencing a few hundred samples a day to around 7,000 per day.

Viral genomics surveillance doesn’t just allow researchers to spot new variants, it helps them learn crucial lessons about how the virus is spreading.

Scientists take advantage of the fact that viruses are constantly making copies of themselves. And every time they make a copy, they may make a little typo in their genetic code. Most of the time, these mutations are meaningless, but they occur at a regular rate. And that makes it possible to make a family tree of the virus. If one viral sample and another have similar typos, researchers can determine they are more closely related.

This can generate key insights.

“In the beginning of the pandemic, we got our hands on some of the first cases that were identified in Connecticut,” says Mary Petrone, a PhD student who works in a molecular biology lab at Yale. Using genomic data, Petrone and her colleagues were able to figure out whether these cases were introduced from abroad, or came from somewhere in the United States. The genetic data revealed that the viruses more closely resembled those circulating on the West Coast than strains from abroad. “It was telling us: there is actually domestic transmission going on,” she says.

Petrone’s lab delivered a key early insight into understanding the virus’s spread in the US. But it wasn’t like the CDC directed them to do so. “Our lab was actually originally set up to do this type of research for mosquito-borne viruses,” she says. “When the pandemic hit we switched over, because there was an urgent public health need to answer some of these questions. So we just happened to really to be set up to do this type of work.”

Setting up more labs to do this work could also help with contact tracing efforts, overall. “For example, if 10 college students test positive,” Julie Segre, a scientist at the National Human Genome Research Institute, writes in an email, “did they come to school already colonized [i.e. infected] or did they transmit the virus while at school.” Genetic evidence can help answer such a question and help prevent future outbreaks.

What needs to happen: coordination, and money

And it’s not necessarily cheap or easy work to do. While the technology that sequences the viral genomes has become relatively inexpensive in recent years (a plug-in USB sequencer will set you back around $1,500), it still takes a lot of skilled lab work to prep samples for analysis. “You definitely don’t need a PhD to be able to do it,” Petrone says. “But you do need to be pretty well trained in molecular biology in the lab. There are a lot of steps where you can contaminate your samples. It can be quite expensive to do.”

Petrone’s lab can do full genome sequencing; that is, they can read every letter of a virus’s genetic code. But not all labs would need to do that to contribute to a surveillance effort. For instance, Petrone’s group is working on a simpler test that can identify the more contagious B117 variant that first was detected in the UK. “That is something you’d be able to run in a clinic,” she says.

But creating a widespread surveillance network for the new variant would require a lot more coordination than what’s currently taking place.

That’s why the US government needs to be more proactive on this, and help set up a nationwide network for genomic data. And that may be coming. According to STAT, the incoming Biden Administration plans to scale up the country’s genomic sequencing efforts as part of a $415 billion emergency Covid-19 spending package it will ask Congress to approve. (Perhaps also auspicious: Biden has selected Eric Lander, a geneticist who co-led the Human Genome Project, to lead the White House Office of Science and Technology Policy, which will be elevated to a Cabinet-level position.)

For a robust genetic surveillance network to be most useful, it needs to be backed up with other rich datasets too. New variants pop up all the time. What matters is whether those variants are linked to worse health outcomes, more reinfections, or faster spread.

“We would ideally have access to good, consistent data about each sample — at the least, geographical location, but more would be better,” Adam Felsenfeld, director of genome sciences at the National Human Genome Research Institute, writes in an email. If possible, too, “one would need details about the medical record of the patients,” he writes, to try to determine if genetic changes in the virus correspond to different disease courses. Again, this would take coordination, as researchers would need informed consent from people to collect this personal data.

A network of viral genome surveillance isn’t just needed for this pandemic, but for future ones too.

“This won’t be the last pandemic,” Griffin says. “If we could get the infrastructure right and get the approach right, then you have things in place you could activate” … for the next time.

For the nearly 100 million people around the world who’ve been infected with the coronavirus, new science offers some comfort: Reinfections appear to be rare, and you may be protected from Covid-19 for at least five months.

The study, the largest of its kind, followed more than 20,000 health workers in the UK, regularly testing them for infection and antibodies. Between June and November, the researchers — from Public Health England (PHE) — found 44 potential reinfections out of the 6,614 participants who had tested positive for antibodies or had a previous positive PCR or antibody test when they joined the study. Meanwhile, of the 14,000-plus people who had tested negative for the virus at the start of the study, there were 409 new infections.

Only two of the 44 potential reinfections were designated “probable” and the rest were considered “possible,” “based on the amount of confirmatory evidence available,” according to the health agency. Fifteen people — or 34 percent — had symptoms.

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So if all 44 reinfections are real, that translates to an 83 percent lower risk of reinfection compared to health workers who never had the virus. If only two are confirmed, that rate of protection goes up to 99 percent. Either way, it suggests natural immunity might provide a similar level of protection as the approved Covid-19 vaccines.

But as with the vaccines, it’s not yet clear how long immunity after an infection lasts. Antibodies may fade after five months or last much longer, something the researchers behind the ongoing study, which will run for a total of 12 months, plan to investigate.

“This [new] study does provide some comfort that naturally acquired antibodies are pretty effective in preventing reinfections,” Akiko Iwasaki, an immunobiologist at Yale University, told Vox. The findings also square with another paper on health workers, published in the New England Journal of Medicine in December: Researchers found people who had Covid-19 antibodies were better protected from the virus for six months than people who did not.

Iwasaki added, “You can also interpret these data to mean that protection against reinfection is not complete — especially for people who had Covid during the first wave, say in March-April 2020.”

People who had the virus may still be able to pass it on if reinfected

The good news for individuals who have had Covid-19 also comes with a warning about the risk they can still pose to other people. While antibodies might protect against a second case of Covid-19 in most people, “early evidence from the next stage of the study suggests that some of these individuals carry high levels of virus and could continue to transmit the virus to others,” PHE warned in its press release.

“We now know that most of those who have had the virus, and developed antibodies, are protected from reinfection, but this is not total,” Susan Hopkins, a senior medical adviser at PHE and the study lead, said in a statement, “and we do not yet know how long protection lasts.”

In other words, even if you’ve had Covid-19, while you’re unlikely to get really sick again anytime soon, you should still consider yourself a potential risk of spreading it to others if you catch the virus again and are asymptomatic. That means continuing to take precautions — like mask-wearing and social distancing, Iwasaki added. And it’s one reason why immunologists have said people who’ve already been infected with the virus should still plan to get the vaccine when their turn comes.

So there’s still a lot more to learn about immunity after Covid-19: How will the new coronavirus variants affect it? Lab data from South Africa, where the 501Y.V2 variant has been spreading, suggests it might be able to escape antibodies produced by prior infections in some people.

Who is most likely to have a strong immune response? We do have some evidence that different individuals mount different antibody responses after Covid-19 infections, but the PHE researchers found no statistically significant difference in rates of protection between people who reported symptoms and those who did not. It’s also possible factors like gender and disease severity influence the strength of a person’s immune response.

For now, though, the research suggests that survivors of the virus might just help us get to herd immunity faster — if their immunity lasts long enough. But given the virus has only been known to humans for a little over a year, it may take a while to authoritatively answer the question.

We knew it was going to be a long, dark winter. But unfortunately, it’s now looking even more grim. Just as the first coronavirus vaccines began rolling out in the US and countries around the world in December — offering hope for the end of the Covid-19 pandemic — two fast-spreading variants of the SARS-CoV-2 virus were discovered in the United Kingdom and South Africa.

Within a matter of weeks, the new variants replaced other versions of the virus in some regions. Scientists say these variants help explain the recent peak in cases in the UK and South Africa that have forced new and tough social distancing measures. They’re also proliferating around the world. As of January 17, the UK variant had been found in 60 countries, and the South Africa variant in 23, according to the World Health Organization.

“It’s scary, isn’t it?” said Richard Lessells, a University of KwaZulu-Natal infectious disease specialist in Durban, South Africa, who co-discovered the South Africa variant. “I’m a Scotsman so talking about my emotions doesn’t come to me naturally but I have a lot of anxiety at the moment.”

All viruses mutate as they move through populations, and until recently, the mutations in SARS-CoV-2 weren’t cause for much concern. (A mutation is a change in the genetic makeup of a virus while a variant is a virus that has a suite of mutations that alter how it behaves.)

B.1.1.7 in the UK and 501Y.V2 in South Africa each have a startling number of changes in the virus’s spike protein, the part that fits into the receptor in human cells, allowing it to infect people — and these changes may be why the new variants are seemingly more contagious than earlier versions of the already contagious virus. (There’s already increasing alarm over variants that have emerged in California and Brazil — and these are just the ones we know about right now.)

While there’s no evidence they cause more severe disease, more cases mean further stress on hospitals and, after that, a rising death rate.

And some researchers have another, pressing worry: These mutations could render the current Covid-19 vaccines less effective. Or they could mean the virus eventually “escapes” them all together. That’s why doctors, virologists, and other health researchers are calling on officials to “vaccinate 24/7 like it’s an emergency,” as Scripps Research scientist Eric Topol said on Twitter. “Because it is.

While vaccine manufacturers like Pfizer and BioNTech say their technologies can readily adapt to changes in the virus, we’re still learning about how the shots will work in this new context — and the mutations in South Africa’s 501Y.V2 are causing particular concern.

As the virus continues to spread and more people are infected, the likelihood of even more dangerous mutations happening rises. So too does the threat the mutations pose to the vaccines. So, without drastic countermeasures, the variants could herald a new, potentially even more difficult, chapter in the pandemic.

Why the new Covid-19 variants are different — and more worrisome — when it comes to the vaccines

Scientists have warned that it was always possible the coronavirus could evolve to evade the Covid-19 vaccines that have been approved so far. The arrival of the UK and South Africa variants may be a step in that direction, increasing the odds of the vaccines becoming less effective over time.

In SARS-CoV-2, the main mutations scientists care about are on the spike protein of the virus — the part that allows it to enter human cells. This is also the protein that Covid-19 vaccines currently available in the US (from Moderna and Pfizer/BioNTech) are designed to imitate. About 4,000 mutations in the SARS-CoV-2 spike protein have been detected at various points in the pandemic. Most haven’t altered the function of the virus and haven’t stirred worry.

In rare cases, a mutation, or several at the same time, lead to changes that give the virus a greater advantage. And that appears to be what’s happening with the UK and South Africa mutation.

The UK variant, B.1.1.7, contains 23 mutations in the genome of the virus while the South Africa variant, 501Y.V2, has at least 21 mutations, with some overlap between the two. In both cases, the changes seem to have increased the fitness of the virus, or its ability to propagate.

“[With genomic sequencing in South Africa] we can show quite clearly there were lots of different lineages circulating prior to October,” Lessells said. “Within the course of just a few weeks, this new lineage — 501Y.V2 — became almost the only lineage you’re detecting.” The story is similar in England, where one in 50 people were infected with Covid-19 as of the new year.

The fact that these mutations became so dominant so quickly suggests that they may be more contagious. Scientists in South Africa think the variant that emerged there is about 50 percent more transmissible, and one estimate suggested the UK variant is up to 70 percent more transmissible.

There could also be other more familiar variables that are driving the spread of these new variants, like holiday travel. Scientists still have to complete experiments in animals to pinpoint differences in transmissibility between these mutations and earlier versions of the virus — and to what extent shifts in peoples’ behavior might also explain the growth in cases.

But they’ve already zeroed in on concerning changes in the virus that are relevant to vaccine effectiveness. With the South Africa variant, for example, one change of particular interest is the E484K mutation in the receptor-binding domain of the virus where it latches on to human cells.

“The E484K mutation has been shown to reduce antibody recognition,” said Francois Balloux, a professor of computational systems biology at the University College London, in a statement. This means it can help the virus “bypass immune protection provided by prior infection or vaccination.”

Researchers have demonstrated how this might happen in cell culture and small human experiments. One, described in a pre-print paper (and therefore not yet peer-reviewed) on Biorxiv, looked at several generations of SARS-CoV-2 challenged with antibody-rich plasma from a Covid-19 convalescent patient and watched to see what happened. At first, the antibodies seemed to beat back the virus. But as the virus mutated, eventually making the E484K substitution, it started to proliferate in spite of the presence of the antibodies.

The senior author on the study, Rino Rappuoli, a professor of vaccines research at Imperial College and chief scientist at GSK, told Vox that when he and his colleagues first ran the experiment, they didn’t know how relevant their findings would be. “But when the South Africa and UK variants came along, we looked at [our data] and saw that, in real life, the first steps of what we saw in vitro are happening.” (GSK has a Covid-19 vaccine in clinical trials with the drugmaker Sanofi.)

Other scientists are coming to similar conclusions. In a second preprint, researchers tracked how mutations altered the effectiveness of the antibody response in people who had the virus. They also found E484K has antibody evasion capabilities. A third, also in test tubes involving survivor plasma from donors in South Africa, showed that antibodies from a prior infection were totally ineffective against the new variant in about half of the donors.

A couple of caveats here: These studies are in vitro, involving the specimens from Covid-19 survivors, rather than antibodies from someone who received a vaccine. We don’t yet know how people in clinical studies who got a vaccine will respond to the new variants.

Still, Rappuoli said, the findings are cause for concern nonetheless. “If given enough time under immune pressure, this virus has the possibility to escape.”

Another preprint study, from researchers in Brazil, recently provided an alarming example of how this could play out. The paper documents the case of a 45-year-old Covid-19 patient with no co-morbidities: months after her first bout with the illness, she was reinfected with a version of SARS-CoV-2 that had the E484K mutation — and experienced more severe illness the second time around. It’s limited evidence, but it suggests that surviving an earlier SARS-CoV-2 infection isn’t a guarantee of protection against variants with this mutation.

“The finding of the E484K, in an episode of SARS-CoV-2 reinfection might have major implications for public health policies, surveillance and immunization strategies,” the authors wrote.

Researchers are racing to figure out how vaccines work against the variants

So what does this mean for the vaccine rollout effort? Will pharmaceutical companies have to tweak their existing vaccines to fight the new variants?

“It is one of the key questions that we are trying to find answers to at the moment, and we have groups around the country working around the clock to get a better understanding of this,” said Lessells. “This also involves collaboration with other groups around the world, with groups running the vaccine trials, with vaccine developers.”

Rappuoli said even if there’s no evidence yet showing the variants can outsmart the immune response created by vaccines, “we should be prepared that at some point in the future that may happen,” he added. For Fred Hutch Cancer Research Center scientist Trevor Bedford, that point could come as early as autumn this year:

Vineet Menachery, a coronavirus researcher at the University of Texas Medical Branch, said the laboratory experiments on SARS-CoV-2 variants represent “the worst-case scenario.”

The currently available vaccines in the US — from Pfizer/BioNTech and Moderna — help the immune system target multiple areas of the spike protein, so the virus would have to change drastically to completely escape the immune response generated by the vaccines. He called the odds of this happening “unlikely but not impossible.”

The diversity of immune responses at the population level gives University of Utah evolutionary virologist Stephen Goldstein some comfort, too. “Our immune systems have evolved to deal with antigenic drift — or the selection of different variants of circulating viruses,” he said. “I’m not worried vaccine efficacy is going to fall off a cliff and go from 95 percent to zero.”

The incoming Centers for Disease Control and Prevention director, Rochelle Walensky, also took comfort in the very high rate of protection the vaccines already have. “The efficacy of the vaccine is so good and so high, that we have a little bit of a cushion,” Walensky said in a January 19 interview with JAMA.

And if the vaccines do turn out to be less effective against the new variants, vaccine developers say they’ll be up for the challenge of adapting them. That’s because the new platforms they’re using can be modified easily to counter new threats.

Vaccine developers say they can adapt their technologies fast

The Pfizer/BioNTech vaccine and the Moderna vaccine both use a molecule called mRNA as their platform to deliver instructions for making the spike protein of SARS-CoV-2. Meanwhile, the vaccine developed by the University of Oxford and AstraZeneca that recently received approval in the UK (but not yet in the US) uses a reprogrammed version of another virus, an adenovirus, to shuttle DNA that codes for the SARS-CoV-2 spike protein.

Human cells then read that DNA or mRNA genetic information and manufacture the spike protein themselves, allowing the immune system to use it for target practice. An advantage of using this approach is that vaccine developers only need to modify DNA or mRNA to tweak the vaccine, something they can do quickly and easily if necessary.

In a January 19 preprint, BioNTech and Pfizer found the UK’s variant may not pose as much of a threat to their vaccine: Antibodies in blood samples from people who got the shot appeared to work against the B.1.1.7’s mutations, making it “unlikely” the variant will escape the vaccine. If a stronger viral foe comes along, BioNTech’s chief executive Ugur Sahin told the FT, “we could manufacture a new vaccine within six weeks.”

These new vaccines would not necessarily require developers to go through every regulatory hurdle again, former FDA chief scientist Jesse Goodman told Vox in December. Instead, new versions of Covid-19 vaccines could end up going through an approval process similar to vaccines for seasonal influenza — with some initial testing but stopping short of massive clinical trials. That means revised Covid-19 vaccines could potentially roll out quickly.

Lessells was cautiously optimistic for another reason: Even if the current vaccines stop working as well as earlier clinical trials suggested, he said, “There are many vaccines in development. So as we learn more about this virus, the vaccine developers also learn from that, and different vaccines may be developed.”

But while it may be possible to alter the vaccine to adapt to new mutations, it’s not ideal: It would require expensive changes in the vaccine production process and eat up valuable time that could be used to inoculate more people during a devastating pandemic.

“From a cost and manufacturing perspective, it would put us far, far behind,” said Anna Durbin, a vaccine researcher and a professor of international health at the Johns Hopkins School of Public Health.

Now’s the time to drive down case numbers and vaccinate

That’s why researchers and health officials are hoping to drive down case numbers and rapidly build up herd immunity with the existing vaccines while also getting ready for changes to the virus that may lay ahead.

To track mutations and understand how they may impact vaccine effectiveness, governments also need to invest more in genomic sequencing, Lessells said. And right now, “there’s a lot of variability around the world in how much sequencing is being done and how people are using sequencing.”

Inadequate sequencing of SARS-CoV-2 genomes may create blind spots where new mutations could be lurking. Infectious disease experts told Stat’s Helen Branswell that the US doesn’t sequence enough and may be unaware of how widespread the UK variant is because of that. According to Lessells, the UK sequences about 10 percent of its cases — on the high end of sequencing volume globally — while the number in South Africa is closer to 1 percent.

Of course, there’s another way to prevent dangerous mutations from arising: preventing cases from happening at all through mask-wearing, social distancing, rapid testing, and treating and isolating infected people. The virus can’t mutate if it’s not replicating inside lots of people.

“The bottom line hasn’t changed: We need to suppress the amount of viral transmission as much as we can,” Goldstein said. Vaccines are a part of that suppression effort, but social distancing and masks are too. According to Salim Abdool Karim, chief adviser on Covid-19 to the South African government, social distancing measures in the country appeared to be bending the curve. “Outbreaks grow exponentially and you’re not going to vaccinate at an exponential rate,” he added. “But you can bring outbreaks down to a rate where they are not growing exponentially.”

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For now, the emergence of the worrisome mutations is a reminder that, despite our collective fatigue, there’s still a long road ahead, Lessells said.

“We keep passing these milestones — going into a new year, having Christmas — and thinking that the virus is going to suddenly do something different because we are celebrating or whatever. Of course, that’s not the case. We are still in the early days. We are still learning about this virus.”