One hesitates to elevate obviously bad arguments, even to point out how bad they are. This is a conundrum that comes up a lot these days, as members of the media measure the utility of reporting on bad faith, disingenuous or simply bizarre claims.
If someone were to insist, for example, that they were not going to get the coronavirus vaccine solely to spite the political left, should that claim be elevated? Can we simply point out how deranged it is to refuse a vaccine that will almost certainly end an international pandemic simply because people with whom you disagree think that maybe this is a good route to end that pandemic? If someone were to write such a thing at some attention-thirsty website, we certainly wouldn’t want to link to it, leaving our own readers having to figure out where it might be found should they choose to do so.
In this case, it’s worth elevating this argument (which, to be clear, is actually floating out there) to point out one of the myriad ways in which the effort to vaccinate as many adults as possible has become interlaced with partisan politics. As the weeks pass and demand for the vaccine has tapered off, the gap between Democratic and Republican interest in being vaccinated seems to be widening — meaning that the end to the pandemic is likely to move that much further into the future.
Consider, for example, the rate of completed vaccinations by county, according to data compiled by CovidActNow. You can see a slight correlation between how a county voted in 2020 — the horizontal axis — and the density of completed vaccinations, shown on the vertical. There’s a greater density of completed vaccinations on the left side of the graph than on the right.
If we shift to the percentage of the population that’s received even one dose of the vaccine, the effect is much more obvious.
This is a relatively recent development. At the beginning of the month, the density of the population that had received only one dose resulted in a graph that looked much like the current density of completed doses.
If we animate those two graphs, the effect is obvious. In the past few weeks, the density of first doses has increased much faster in more-Democratic counties.
If we group the results of the 2020 presidential contest into 20-point buckets, the pattern is again obvious.
It’s not a new observation that Republicans are less willing to get the vaccine; we’ve reported on it repeatedly. What’s relatively new is how that hesitance is showing up in the actual vaccination data.
A Post-ABC News poll released on Monday showed that this response to the vaccine holds even when considering age groups. We’ve known for a while that older Americans, who are more at risk from the virus, have been more likely to seek the vaccine. But even among seniors, Republicans are significantly more hesitant to receive the vaccine than are Democrats.
This is a particularly dangerous example of partisanship. People 65 or older have made up 14 percent of coronavirus infections, according to federal data, but 81 percent of deaths. That’s among those for whom ages are known, a subset (though a large majority) of overall cases. While about 1.8 percent of that overall group has died, the figure for those aged 65 and over is above 10 percent.
As vaccines have been rolled out across the country, you can see how more-heavily-blue counties have a higher density of vaccinations in many states.
This is not a universal truth, of course. Some heavily Republican counties have above-average vaccination rates. (About 40 percent of counties that preferred former president Donald Trump last year are above the average in the CovidActNow data. The rate among Democratic counties is closer to 80 percent.) But it is the case that there is a correlation between how a county voted and how many of its residents have been vaccinated. It is also the case that the gap between red and blue counties is widening.
Given all of that, it probably makes sense to point out that an argument against vaccines based on nothing more than “lol libs will hate this” is an embarrassing argument to make.
In this last episode of our six-part series on vaccinations, supported by the National Institute for Health Care Management Foundation, we cover vaccine development – particularly in the context of the current global pandemic. We discuss the timeline of Covid-19 vaccine development and the mRNA vaccine approach.
She grew up in Hungary, daughter of a butcher. She decided she wanted to be a scientist, although she had never met one. She moved to the United States in her 20s, but for decades never found a permanent position, instead clinging to the fringes of academia.
Now Katalin Kariko, 66, known to colleagues as Kati, has emerged as one of the heroes of Covid-19 vaccine development. Her work, with her close collaborator, Dr. Drew Weissman of the University of Pennsylvania, laid the foundation for the stunningly successful vaccines made by Pfizer-BioNTech and Moderna.
For her entire career, Dr. Kariko has focused on messenger RNA, or mRNA — the genetic script that carries DNA instructions to each cell’s protein-making machinery. She was convinced mRNA could be used to instruct cells to make their own medicines, including vaccines.
But for many years her career at the University of Pennsylvania was fragile. She migrated from lab to lab, relying on one senior scientist after another to take her in. She never made more than $60,000 a year.
By all accounts intense and single-minded, Dr. Kariko lives for “the bench” — the spot in the lab where she works. She cares little for fame. “The bench is there, the science is good,” she shrugged in a recent interview. “Who cares?”
Dr. Anthony Fauci, director of the National Institutes of Allergy and infectious Diseases, knows Dr. Kariko’s work. “She was, in a positive sense, kind of obsessed with the concept of messenger RNA,” he said.
Dr. Kariko’s struggles to stay afloat in academia have a familiar ring to scientists. She needed grants to pursue ideas that seemed wild and fanciful. She did not get them, even as more mundane research was rewarded.
“When your idea is against the conventional wisdom that makes sense to the star chamber, it is very hard to break out,” said Dr. David Langer, a neurosurgeon who has worked with Dr. Kariko.
Dr. Kariko’s ideas about mRNA were definitely unorthodox. Increasingly, they also seem to have been prescient.
“It’s going to be transforming,” Dr. Fauci said of mRNA research. “It is already transforming for Covid-19, but also for other vaccines. H.I.V. — people in the field are already excited. Influenza, malaria.”
‘I Felt Like a God’
For Dr. Kariko, most every day was a day in the lab. “You are not going to work — you are going to have fun,” her husband, Bela Francia, manager of an apartment complex, used to tell her as she dashed back to the office on evenings and weekends. He once calculated that her endless workdays meant she was earning about a dollar an hour.
For many scientists, a new discovery is followed by a plan to make money, to form a company and get a patent. But not for Dr. Kariko. “That’s the furthest thing from Kate’s mind,” Dr. Langer said.
She grew up in the small Hungarian town of Kisujszallas. She earned a Ph.D. at the University of Szeged and worked as a postdoctoral fellow at its Biological Research Center.
In 1985, when the university’s research program ran out of money, Dr. Kariko, her husband, and 2-year-old daughter, Susan, moved to Philadelphia for a job as a postdoctoral student at Temple University. Because the Hungarian government only allowed them to take $100 out of the country, she and her husband sewed £900 (roughly $1,246 today) into Susan’s teddy bear. (Susan grew up to be a two-time Olympic gold medal winner in rowing.)
When Dr. Kariko started, it was early days in the mRNA field. Even the most basic tasks were difficult, if not impossible. How do you make RNA molecules in a lab? How do you get mRNA into cells of the body?
In 1989, she landed a job with Dr. Elliot Barnathan, then a cardiologist at the University of Pennsylvania. It was a low-level position, research assistant professor, and never meant to lead to a permanent tenured position. She was supposed to be supported by grant money, but none came in.
She and Dr. Barnathan planned to insert mRNA into cells, inducing them to make new proteins. In one of the first experiments, they hoped to use the strategy to instruct cells to make a protein called the urokinase receptor. If the experiment worked, they would detect the new protein with a radioactive molecule that would be drawn to the receptor.
“Most people laughed at us,” Dr. Barnathan said.
One fateful day, the two scientists hovered over a dot-matrix printer in a narrow room at the end of a long hall. A gamma counter, needed to track the radioactive molecule, was attached to a printer. It began to spew data.
Their detector had found new proteins produced by cells that were never supposed to make them — suggesting that mRNA could be used to direct any cell to make any protein, at will.
“I felt like a god,” Dr. Kariko recalled.
She and Dr. Barnathan were on fire with ideas. Maybe they could use mRNA to improve blood vessels for heart bypass surgery. Perhaps they could even use the procedure to extend the life span of human cells.
Dr. Barnathan, though, soon left the university, accepting a position at a biotech firm, and Dr. Kariko was left without a lab or financial support. She could stay at Penn only if she found another lab to take her on. “They expected I would quit,” she said.
Universities only support low-level Ph.D.s for a limited amount of time, Dr. Langer said: “If they don’t get a grant, they will let them go.” Dr. Kariko “was not a great grant writer,” and at that point “mRNA was more of an idea,” he said.
But Dr. Langer knew Dr. Kariko from his days as a medical resident, when he had worked in Dr. Barnathan’s lab. Dr. Langer urged the head of the neurosurgery department to give Dr. Kariko’s research a chance. “He saved me,” she said.
Dr. Langer thinks it was Dr. Kariko who saved him — from the kind of thinking that dooms so many scientists.
Working with her, he realized that one key to real scientific understanding is to design experiments that always tell you something, even if it is something you don’t want to hear. The crucial data often come from the control, he learned — the part of the experiment that involves a dummy substance for comparison.
“There’s a tendency when scientists are looking at data to try to validate their own idea,” Dr. Langer said. “The best scientists try to prove themselves wrong. Kate’s genius was a willingness to accept failure and keep trying, and her ability to answer questions people were not smart enough to ask.”
Dr. Langer hoped to use mRNA to treat patients who developed blood clots following brain surgery, often resulting in strokes. His idea was to get cells in blood vessels to make nitric oxide, a substance that dilates blood vessels, but has a half-life of milliseconds. Doctors can’t just inject patients with it.
He and Dr. Kariko tried their mRNA on isolated blood vessels used to study strokes. It failed. They trudged through snow in Buffalo, N.Y., to try it in a laboratory with rabbits prone to strokes. Failure again.
And then Dr. Langer left the university, and the department chairman said he was leaving as well. Dr. Kariko again was without a lab and without funds for research.
A meeting at a photocopying machine changed that. Dr. Weissman happened by, and she struck up a conversation. “I said, ‘I am an RNA scientist — I can make anything with mRNA,’” Dr. Kariko recalled.
Dr. Weissman told her he wanted to make a vaccine against H.I.V. “I said, ‘Yeah, yeah, I can do it,’” Dr. Kariko said.
Despite her bravado, her research on mRNA had stalled. She could make mRNA molecules that instructed cells in petri dishes to make the protein of her choice. But the mRNA did not work in living mice.
“Nobody knew why,” Dr. Weissman said. “All we knew was that the mice got sick. Their fur got ruffled, they hunched up, they stopped eating, they stopped running.”
It turned out that the immune system recognizes invading microbes by detecting their mRNA and responding with inflammation. The scientists’ mRNA injections looked to the immune system like an invasion of pathogens.
But with that answer came another puzzle. Every cell in every person’s body makes mRNA, and the immune system turns a blind eye. “Why is the mRNA I made different?” Dr. Kariko wondered.
A control in an experiment finally provided a clue. Dr. Kariko and Dr. Weissman noticed their mRNA caused an immune overreaction. But the control molecules, another form of RNA in the human body — so-called transfer RNA, or tRNA — did not.
A molecule called pseudouridine in tRNA allowed it to evade the immune response. As it turned out, naturally occurring human mRNA also contains the molecule.
Added to the mRNA made by Dr. Kariko and Dr. Weissman, the molecule did the same — and also made the mRNA much more powerful, directing the synthesis of 10 times as much protein in each cell.
The idea that adding pseudouridine to mRNA protected it from the body’s immune system was a basic scientific discovery with a wide range of thrilling applications. It meant that mRNA could be used to alter the functions of cells without prompting an immune system attack.
“We both started writing grants,” Dr. Weissman said. “We didn’t get most of them. People were not interested in mRNA. The people who reviewed the grants said mRNA will not be a good therapeutic, so don’t bother.’”
Leading scientific journals rejected their work. When the research finally was published, in Immunity, it got little attention.
Dr. Weissman and Dr. Kariko then showed they could induce an animal — a monkey — to make a protein they had selected. In this case, they injected monkeys with mRNA for erythropoietin, a protein that stimulates the body to make red blood cells. The animals’ red blood cell counts soared.
The scientists thought the same method could be used to prompt the body to make any protein drug, like insulin or other hormones or some of the new diabetes drugs. Crucially, mRNA also could be used to make vaccines unlike any seen before.
Instead of injecting a piece of a virus into the body, doctors could inject mRNA that would instruct cells to briefly make that part of the virus.
“We talked to pharmaceutical companies and venture capitalists. No one cared,” Dr. Weissman said. “We were screaming a lot, but no one would listen.”
Eventually, though, two biotech companies took notice of the work: Moderna, in the United States, and BioNTech, in Germany. Pfizer partnered with BioNTech, and the two now help fund Dr. Weissman’s lab.
‘Oh, It Works’
Soon clinical trials of an mRNA flu vaccine were underway, and there were efforts to build new vaccines against cytomegalovirus and the Zika virus, among others. Then came the coronavirus.
Researchers had known for 20 years that the crucial feature of any coronavirus is the spike protein sitting on its surface, which allows the virus to inject itself into human cells. It was a fat target for an mRNA vaccine.
Chinese scientists posted the genetic sequence of the virus ravaging Wuhan in January 2020, and researchers everywhere went to work. BioNTech designed its mRNA vaccine in hours; Moderna designed its in two days.
The idea for both vaccines was to introduce mRNA into the body that would briefly instruct human cells to produce the coronavirus’s spike protein. The immune system would see the protein, recognize it as alien, and learn to attack the coronavirus if it ever appeared in the body.
The vaccines, though, needed a lipid bubble to encase the mRNA and carry it to the cells that it would enter. The vehicle came quickly, based on 25 years of work by multiple scientists, including Pieter Cullis of the University of British Columbia.
Scientists also needed to isolate the virus’s spike protein from the bounty of genetic data provided by Chinese researchers. Dr. Barney Graham, of the National Institutes of Health, and Jason McClellan, of the University of Texas at Austin, solved that problem in short order.
Testing the quickly designed vaccines required a monumental effort by companies and the National Institutes of Health. But Dr. Kariko had no doubts.
On Nov. 8, the first results of the Pfizer-BioNTech study came in, showing that the mRNA vaccine offered powerful immunity to the new virus. Dr. Kariko turned to her husband. “Oh, it works,” she said. “I thought so.”
To celebrate, she ate an entire box of Goobers chocolate-covered peanuts. By herself.
Dr. Weissman celebrated with his family, ordering takeout dinner from an Italian restaurant, “with wine,” he said. Deep down, he was awed.
“My dream was always that we develop something in the lab that helps people,” Dr. Weissman said. “I’ve satisfied my life’s dream.”
Dr. Kariko and Dr. Weissman were vaccinated on Dec. 18 at the University of Pennsylvania. Their inoculations turned into a press event, and as the cameras flashed, she began to feel uncharacteristically overwhelmed.
A senior administrator told the doctors and nurses rolling up their sleeves for shots that the scientists whose research made the vaccine possible were present, and they all clapped. Dr. Kariko wept.
Things could have gone so differently, for the scientists and for the world, Dr. Langer said. “There are probably many people like her who failed,” he said.
President Joe Biden proposed an ambitious budget for the next federal fiscal year that includes more money for fighting the opioid epidemic, bolstering public health and several other healthcare items.
The budget request to Congress, released Friday, acts as essentially a wish list of priorities for the administration for the next year.
It is doubtful how much would get approved by Congress but sends a message of what the administration prioritizes.
Here are three healthcare priorities outlined in the request:
The opioid epidemic:$10.7 billion was requested for fighting the opioid epidemic, $3.9 billion over the 2021 enacted level. The money will help support research, prevention and recovery services. The administration also is calling for targeted investments for “populations with unique needs, including Native Americans, older Americans and rural populations,” according to a release from the Office of Management and Budget on Friday.
Public health infrastructure:$8.7 billion was requested for the Centers for Disease Control and Prevention to boost public health capacity in states and territories. OMB calls the budget increase the largest in nearly two decades for the agency at the frontlines of combating COVID-19. The Biden administration hopes to use the new money to train new epidemiologists and public health experts and “build international capacity to detect, prepare for and respond to emerging global threats.” A letter sent Friday to congressional leaders from the White House said that CDC funding was 10% lower than the previous decade after adjusting for inflation.
Research funding boosts:$6.5 billion to launch a new agency called the Advanced Research Projects Agency for Health. The new agency would provide major increases in federal research and development spending on cancer and other diseases such as diabetes and Alzheimer’s. The goal of the investment is to “drive transformational innovation in health research and speed application and implementation of health breakthroughs,” OMB’s letter to Congress said. The funding is rolled into a $51 billion request for funding to the National Institutes of Health.
A new report out later today concludes that basic scientific research plays an essential role in creating companies that later produce thousands of jobs and billions in economic value.
Why it matters: The report uses thepandemic — and especially the rapid development of new mRNA vaccines — to show how basic research funding from the government lays the necessary groundwork for economically valuable companies down the road.
By the numbers: The Science Coalition — a nonprofit group that represents 50 of the nation’s top private and public research universities — identified 53 companies that have spun off from federally funded university research.
Those companies — which range from pharmaceutical startups to agriculture firms — have contributed more than $1.3 billion to U.S. GDP between 2015 and 2019, while supporting the creation of more than 100,000 jobs.
What they’re saying:“The COVID-19 pandemic has shown that the need for the federal government to continue investing in fundamental research is far from theoretical,” says John Latini, president of the Science Coalition. “Consistent, sustained, robust federal funding is how science evolves.”
The National Oceanic and Atmospheric Administration would see its budget rise to a record high of $6.9 billion, including $800 millionreserved for climate research.
The catch: The Biden budget proposal is just that, and it will ultimately be up to Congress to decide how much to allocate to research agencies.
Context: Government research funding is vital because private money tends to go to applied research. But without basic research — the lifeblood of science — the U.S. risks missing out on potentially world-changing innovations in the future.
The long-term value of that funding can be seen in the story of Katalin Kariko, an obscure biomedical researcher who labored for years on mRNA with little reward — until the pandemic, when her work helped provide the foundation for mRNA COVID-19 vaccines.
The bottom line: Because its ultimate payoff might lay years in the future, it’s easy to see basic research funding as a waste — until the day comes when we need it.
Wealthy nations — including the U.S., the U.K. and the EU — have vaccinated their citizens at a rate of one person per second over the last month, while most developing countries still haven’t administered a single shot, according to the People’s Vaccine Alliance.
Why it matters:As higher-income countries aim to achieve herd immunity in a matter of months, most of the world’s vulnerable people will remain unprotected.
Experts say that mutations that may arise while the virus spreads could be a danger to us all, vaccinated or not.
The big picture: Even though more vaccines will arrive in developing nations soon, only 3% of people in those countries are likely to be vaccinated by mid-2021.
At best, only a fifth of their population will be vaccinated by the end of the year, per the People’s Vaccine Alliance.
What we’re watching: Three dozen countries have bought several times the amount of vaccine that they’ll need to vaccinate their entire population.
The U.S. alone has ordered more than a billion extra doses, Science Magazine reports. Global health leaders are saying it’s time to figure out where all of these excess doses will go.
“Over the next year or two, U.S. surplus doses and those from other countries could add up to enough to immunize everyone in the many poorer nations that lack any secured COVID-19 vaccine,” Science writes.
One year after the World Health Organization declared COVID-19 a pandemic, the end of that pandemic is within reach.
The big picture:The death and suffering caused by the coronavirus have been much worse than many people expected a year ago — but the vaccines have been much better.
Flashback: “Bottom line, it’s going to get worse,” Anthony Fauci told a congressional panel on March 11, 2020, the day the WHO formally declared COVID-19 to be a global pandemic.
A year ago today, the U.S. had confirmed 1,000 coronavirus infections. Now we’re approaching 30 million.
In the earliest days of the pandemic, Americans were terrified by the White House’s projections — informed by well-respected modeling — that 100,000 to 240,000 Americans could die from the virus. That actual number now sits at just under 530,000.
Many models at the time thought the virus would peak last May. It was nowhere close to its height by then. The deadliest month of the pandemic was January.
Yes, but: Last March, even the sunniest optimists didn’t expect the U.S. to have a vaccine by now.
They certainly didn’t anticipate that over 300 million shots would already be in arms worldwide, and they didn’t think the eventual vaccines, whenever they arrived, would be anywhere near as effective as these shots turned out to be.
Where it stands: President Biden has said every American adult who wants a vaccine will be able to get one by the end of May, and the country is on track to meet that target.
The U.S. is administering over 2 million shots per day, on average. Roughly 25% of the adult population has gotten at least one shot.
The federal government has purchased more doses than this country will be able to use: 300 million from Pfizer, 300 million from Moderna and 200 million from Johnson & Johnson.
The Pfizer and Moderna orders alone would be more than enough to fully vaccinate every American adult. (The vaccines aren’t yet authorized for use in children.)
Yes, millions of Americans are still anxiously awaiting their first shot — and navigating signup websites that are often frustrating and awful.
But the supply of available vaccines is expected to surge this month, and the companies say the bulk of those doses should be available by the end of May.
Cases, hospitalizations and deaths are all falling sharply at the same time vaccinations are ramping up.
The bottom line: Measured in death, loss, isolation and financial ruin, one year has felt like an eternity. Measured as the time between the declaration of a pandemic and vaccinating 60 million Americans, one year is an instant.
The virus hasn’t been defeated, and may never fully go away. Getting back to “normal” will be a moving target. Nothing’s over yet. But the end of the worst of it — the long, brutal nightmare of death and suffering — is getting close.
AstraZeneca on Monday became the third pharmaceutical company to announce remarkable results from late-stage trials of a coronavirus vaccine, saying that its candidate, developed by Oxford University, is up to 90 percent effective.
This is the third straight week to begin with buoyant scientific news that suggests, even as coronavirus cases surge to devastating levels in many countries, an end to the pandemic is in sight.
Pfizer and its German partner BioNTech and Moderna have each reported vaccines that are 95 percent effective in clinical trials. A direct comparison to the Oxford-AstraZeneca vaccine is complicated, due to the trial design, but the vaccine may be a more realistic option for much of the world, as it is likely to be cheaper and does not need to be stored at subzero temperatures.
Peter Piot, director of the London School of Hygiene & Tropical Medicine, who was instrumental in the battle against AIDS, said the positive results from three vaccine candidates cannot be overestimated.
“2020 will be remembered for the many lives lost from covid-19, lockdowns and the U.S. election. Science should now be added to this list,” said Piot, adding, “the only way to stop covid-19 in its tracks is having multiple effective and safe vaccines that can be deployed all around the world and in vast quantities.”
“I’m totally delighted,” said Hildegund C.J. Ertl, a vaccine expert at the Wistar Institute in Philadelphia. Adding to the results from Pfizer and Moderna, “what it tells me is this virus can be beaten quite easily: 90 to 95 percent efficacy is something we’d dream about for influenza virus, and we’d never get it.”
The Oxford-AstraZeneca team said in a video conference with journalists that its candidate offered 90 percent protection against the virus when a subject received a half-dose, followed with a full dose one month later. Efficacy was lower — 62 percent — when subjects received two full doses a month apart. The interim results, therefore, averaged to 70 percent efficacy.
Andrew Pollard, chief investigator of the Oxford trial, said the findings showed the vaccine would save many lives.
“Excitingly, we’ve found that one of our dosing regimens may be around 90 percent effective, and if this dosing regimen is used, more people could be vaccinated with planned vaccine supply,” he said.
Britain has preordered 100 million doses — which at a dose and a half per person would cover most of its population. The United States has ordered 300 million.
The results have yet to be peer-reviewed or published, and will be scrutinized by regulators. Many questions remain, including whether the vaccine can reduce transmission of the virus by people without symptoms, which would have repercussions for how soon people could stop wearing masks. It is also unclear how long the immunity from the vaccine lasts — a crucial question.
Sarah Gilbert, a lead Oxford researcher, cautioned that the dose-and-a-half regimen would have to be more closely studied to be fully understood. But she said the first half-dose might be priming a person’s immune system just enough, and that the second booster then encourages the body to produce a robust defense against sickness and infection.
AstraZeneca and Oxford have been conducting Phase 3 clinical trials worldwide, with the most recent data coming from an interim analysis based on 131 coronavirus infections in Britain and Brazil among 10,000 volunteers, with half getting the vaccine and half getting a placebo.
The company said it would present the results to Britain’s health-care products regulators immediately and would seek approval to fine-tune its clinical trials in the United States, to further assess the half-dose shot followed by a booster.
Because the vaccine is already in production, if approved, the first 4 million doses could be ready in December, and 40 million could be delivered in the first quarter of 2021, company executives said. By the spring, the company and its global partners in India, Brazil, Russia and the United States could be cranking out 100 million to 200 million doses a month.
British Health Secretary Matt Hancock said “should all that go well, the bulk of the rollout will be in the new year.”
In a statement to Parliament, Prime Minister Boris Johnson said that vaccines were “edging ever closer to liberating us from the virus, demonstrating emphatically that this is not a pandemic without end. We can take great heart from today’s news, which has the makings of a wonderful British scientific achievement.”
World markets have rallied on optimistic vaccine news, though shares in AstraZeneca were down Monday on the London stock exchange.
No participants who received the vaccine developed severe cases or required hospitalization, AstraZeneca said Monday. The drugmaker also said that no “serious safety events” were reported in connection with the vaccine, which was typically “well tolerated” by participants regardless of their dosing levels or ages.
The vaccine uses a harmless cold virus that typically infects chimpanzees to deliver to the body’s cells the genetic code of the spike protein that dots the outside of the coronavirus. That teaches the body’s immune system to recognize and block the real virus.
Although the reason the regimen with an initial half-dose worked better remains to be teased out, Ertl said that it could be related to the fact that the body’s immune system can develop a defense system to block the harmless virus that’s used to deliver the spike protein’s code. Giving a smaller initial dose may lessen those defenses, and make the vaccine more effective.
Several other vaccines in late-stage development use a similar technology, harnessing a harmless virus to deliver a payload that will teach the immune system how to fight off the real thing — including the Johnson & Johnson vaccine, the Russian vaccine being developed by the Gamaleya Research Institute and the vaccine made by CanSino Biologics in China.
While the results released by AstraZeneca indicate somewhat lower efficacy than Pfizer and Moderna, the vaccine can be stored and transported at normal refrigerated conditions for up to six months. That could make it significantly easier to roll out than Pfizer’s vaccine, which has to be stored at minus-70 degrees Celsius, or Moderna’s, which is stable in refrigerated conditions for only 30 days and must be frozen at minus-20 degrees Celsius after that.
The Oxford-AstraZeneca vaccine was first developed in a small laboratory running on a shoestring budget by Gilbert at Oxford and her team. The university kicked in 1 million pounds ($1.3 million) and then sought a manufacturing partner, before settling on AstraZeneca.
“We wanted to ensure there wouldn’t be any profiteering off the pandemic,” said Louise Richardson, the university’s vice chancellor, so that their vaccine would be widely distributed “and wouldn’t just be for the wealthy and the first world.”
The scientists said that although it appeared to be a race, or a competition, among the front-running vaccine developers, no one company could produce by itself the millions of doses needed to end the pandemic.
“We don’t have enough supply for the whole planet,” Pollard said, adding that the important message is that today there are at least three highly effective, safe vaccines, that also appear to work well among the elderly, and that they are produced using different technologies, ensuring the quickest route to manufacture the billions of doses that will be necessary.
Pollard said it is “unclear why” the different vaccines were producing different results, and he said he and the scientific community awaited full data sets from all the clinical trials to fully understand what is going on. He said different studies were also using different end points to describe efficacy.
“At this moment we can’t fully explain the differences,” Pollard said. “It’s critical to understand what everyone is measuring.”
Once again, the coronavirus is ascendant. As infections mount across the country, it is dawning on Americans that the epidemic is now unstoppable, and that no corner of the nation will be left untouched.
As of Wednesday, the pathogen had infected at least 4.3 million Americans, killing more than 150,000. Many experts fear the virus could kill 200,000 or even 300,000 by year’s end. Even President Trump has donned a mask, after resisting for months, and has canceled the Republican National Convention celebrations in Florida.
Each state, each city has its own crisis driven by its own risk factors: vacation crowds in one, bars reopened too soon in another, a revolt against masks in a third.
“We are in a worse place than we were in March,” when the virus coursed through New York, said Dr. Leana S. Wen, a former Baltimore health commissioner. “Back then we had one epicenter. Now we have lots.”
To assess where the country is heading now, The New York Times interviewed 20 public health experts — not just clinicians and epidemiologists, but also historians and sociologists, because the spread of the virus is now influenced as much by human behavior as it is by the pathogen itself.
While there may be no appetite for a national lockdown, local restrictions must be tightened when required, the researchers said, and governors and mayors must have identical goals. Testing must become more targeted.
In most states, contact tracing is now moot — there are simply too many cases to track. And while progress has been made on vaccines, none is expected to arrive this winter in time to stave off what many fear will be a new wave of deaths.
“We’re all incredibly depressed and in shock at how out of control the virus is in the U.S.,” said Dr. Michele Barry, the director of the Center for Innovation in Global Health at Stanford University.
With so much wealth and medical talent, they asked, how could we have done so poorly? How did we fare not just worse than autocratic China and isolated New Zealand, but also worse than tiny, much poorer nations like Vietnam and Rwanda?
“National hubris and belief in American exceptionalism have served us badly,” said Martha L. Lincoln, a medical anthropologist and historian at San Francisco State University. “We were not prepared to see the risk of failure.”
What We’ve Learned
Since the coronavirus was first found to be the cause of lethal pneumonias in Wuhan, China, in late 2019, scientists have gained a better understanding of the enemy.
The infection may start in the lungs, but it is very different from influenza, a respiratory virus. In severely ill patients, the coronavirus may attach to receptors inside the veins and arteries, and move on to attack the kidneys, the heart, the gut and even the brain, choking off these organs with hundreds of tiny blood clots.
Among adults, a very different picture has emerged. Growing evidence suggests that perhaps 10 percent of the infected account for 80 percent of new transmissions. Unpredictable superspreading events in nursing homes, meatpacking plants, churches, prisons and bars are major drivers of the epidemic.
One or even several vaccines may be available by year’s end, which would be a spectacular achievement. But by then the virus may have in its grip virtually every village and city on the globe.
Solutions Must Be Localized
Some experts, like Michael T. Osterholm, the director of the University of Minnesota’s Center for Infectious Disease Research and Policy, argue that only a nationwide lockdown can completely contain the virus now. Other researchers think that is politically impossible, but emphasize that localities must be free to act quickly and enforce strong measures with support from their state legislators.
Danielle Allen, the director of Harvard University’s Edmond J. Safra Center for Ethics, which has issued pandemic response plans, said that finding less than one case per 100,000 people means a community should continue testing, contact tracing and isolating cases — with financial support for those who need it.
Up to 25 cases per 100,000 requires greater restrictions, like closing bars and limiting gatherings. Above that number, authorities should issue stay-at-home orders, she said.
Testing must be focused, not just offered at convenient parking lots, experts said, and it should be most intense in institutions like nursing homes, prisons, factories or other places at risk of superspreading events.
Testing must be free in places where people are poor or uninsured, such as public housing projects, Native American reservations and churches and grocery stores in impoverished neighborhoods.
None of this will be possible unless the nation’s capacity for testing, a continuing disaster, is greatly expanded. By the end of summer, the administration hopes to start using “pooling,” in which tests are combined in batches to speed up the process.
But the method only works in communities with lower infection rates, where large numbers of pooled tests turn up relatively few positive results. It fails where the virus has spread everywhere, because too many batches turn up positive results that require retesting.
Above all, researchers said, mask use should be universal indoors — including airplanes, subway cars and every other enclosed space — and outdoors anywhere people are less than six feet apart.
Dr. Emily Landon, an infection control specialist at the University of Chicago Pritzker School of Medicine, said it was “sad that something as simple as a mask got politicized.”
“It’s not a statement, it’s a piece of clothing,” she added. “You get used to it the way you got used to wearing pants.”
Arguments that masks infringe on personal rights must be countered both by legal orders and by persuasion. “We need more credible messengers endorsing masks,” Dr. Wen said — just before the president himself became a messenger.
“They could include C.E.O.s or celebrities or religious leaders. Different people are influencers to different demographics.”
Although this feels like a new debate, it is actually an old one. Masks were common in some Western cities during the 1918 flu pandemic and mandatory in San Francisco. There was even a jingle: “Obey the laws, wear the gauze. Protect your jaws from septic paws.”
“A libertarian movement, the Anti-Mask League, emerged,” Dr. Lincoln of San Francisco State said. “There were fistfights with police officers over it.” Ultimately, city officials “waffled” and compliance faded.
“I wonder what this issue would be like today,” she mused, “if that hadn’t happened.”
Images of Americans disregarding social distancing requirements have become a daily news staple. But the pictures are deceptive: Americans are more accepting of social distancing than the media sometimes portrays, saidBeth Redbird, a Northwestern University sociologist who since March has conducted regular surveys of 8,000 adults about the impact of the virus.
“About 70 percent of Americans report using all forms of it,” she said. “And when we give them adjective choices, they describe people who won’t distance as mean, selfish or unintelligent, not as generous, open-minded or patriotic.”
The key predictor, she said in early July, was whether or not the poll respondent trusted Mr. Trump. Those who trusted him were less likely to practice social distancing. That was true of Republicans and independents, “and there’s no such thing as a Democrat who trusts Donald Trump,” she added.
Whether or not people support coercive measures like stay-at-home orders or bar closures depended on how scared the respondent was.
“When rising case numbers make people more afraid, they have more taste for liberty-constraining actions,” Dr. Redbird said. And no economic recovery will occur, she added, “until people aren’t afraid. If they are, they won’t go out and spend money even if they’re allowed to.”
The Danger Indoors
As of Wednesday, new infections were rising in 33 states, and in Puerto Rico and the District of Columbia, according to a database maintained by The Times.
Weeks ago, experts like Dr. Anthony S. Fauci, the director of the National Institute for Allergy and Infectious Diseases, were advising states where the virus was surging to pull back from reopening by closing down bars, forbidding large gatherings and requiring mask usage.
Many of those states are finally taking that advice, but it is not yet clear whether this national change of heart has happened in time to stop the newest wave of deaths from ultimately exceeding the 2,750-a-day peak of mid-April. Now, the daily average is 1,106 virus deaths nationwide.
Deaths may surge even higher, experts warned, when cold weather, rain and snow force Americans to meet indoors, eat indoors and crowd into public transit.
Oddly, states that are now hard-hit might become safer, some experts suggested. In the South and Southwest, summers are so hot that diners seek air-conditioning indoors, but eating outdoors in December can be pleasant.
Several studies have confirmed transmission in air-conditioned rooms. In one well-known case cluster in a restaurant in Guangzhou, China, researchers concluded that air-conditioners blew around a viral cloud, infecting patrons as far as 10 feet from a sick diner.
Rural areas face another risk. Almost 80 percent of the country’s counties lack even one infectious disease specialist, according to a study led by Dr. Rochelle Walensky, the chief of infectious diseases at Massachusetts General Hospital in Boston.
At the moment, the crisis is most acute in Southern and Southwestern states. But websites that track transmission rates show that hot spots can turn up anywhere. For three weeks, for example, Alaska’s small outbreak has been one of the country’s fastest-spreading, while transmission in Texas and Arizona has dramatically slowed.
Deaths now may rise more slowly than they did in spring, because hospitalized patients are, on average, younger this time. But overwhelmed hospitals can lead to excess deaths from many causes all over a community, as ambulances are delayed and people having health crises avoid hospitals out of fear.
The experts were divided as to what role influenza will play in the fall. A harsh flu season could flood hospitals with pneumonia patients needing ventilators. But some said the flu season could be mild or almost nonexistent this year.
Normally, the flu virus migrates from the Northern Hemisphere to the Southern Hemisphere in the spring — presumably in air travelers — and then returns in the fall, with new mutations that may make it a poor match for the annual vaccine.
Assuming there is still little air travel to the United States this fall, there may be little “reseeding” of the flu virus here. But in case that prediction turns out be wrong, all the researchers advised getting flu shots anyway.
“There’s no reason to be caught unprepared for two respiratory viruses,” said Tara C. Smith, an epidemiologist at Kent State University’s School of Public Health.
Partially Effective Remedies
Experts familiar with vaccine and drug manufacturing were disappointed that, thus far, only dexamethasone and remdesivir have proved to be effective treatments, and then only partially.
Most felt that monoclonal antibodies — cloned human proteins that can be grown in cell culture — represented the best hope until vaccines arrive. Regeneron, Eli Lilly and other drugmakers are working on candidates.
“They’re promising both for treatment and for prophylaxis, and there are companies with track records and manufacturing platforms,” said Dr. Luciana Borio, a former director of medical and biodefense preparedness at the National Security Council. “But manufacturing capacity is limited.”
Because the virus is still spreading rapidly, most experts said “challenge trials,” in which a small number of volunteers are vaccinated and then deliberately infected, would probably not be needed.
Absent a known cure, “challenges” can be ethically fraught, and some doctors oppose doing them for this virus. “They don’t tell you anything about safety,” Dr. Borio said.
And when a virus is circulating unchecked, a typical placebo-controlled trial with up to 30,000 participants can be done efficiently, she added. Moderna and Pfizer have already begun such trials.
The Food and Drug Administration has said a vaccine will pass muster even if it is only 50 percent effective. Experts said they could accept that, at least initially, because the first vaccine approved could save lives while testing continued on better alternatives.
“A vaccine doesn’t have to work perfectly to be useful,” Dr. Walensky said. “Even with measles vaccine, you can sometimes still get measles — but it’s mild, and you aren’t infectious.”
“We don’t know if a vaccine will work in older folks. We don’t know exactly what level of herd immunity we’ll need to stop the epidemic. But anything safe and fairly effective should help.”
No matter what state the virus reaches, one risk remains constant. Even in states with few Black and Hispanic residents, they are usually hit hardest, experts said.
People of color are more likely to have jobs that require physical presence and sometimes close contact, such as construction work, store clerking and nursing. They are more likely to rely on public transit and to live in neighborhoods where grocery stores are scarce and crowded.
Federal data gathered through May 28 shows that Black and Hispanic Americans were three times as likely to get infected as their white neighbors, and twice as likely to die, even if they lived in remote rural counties with few Black or Hispanic residents.
“By the time that minority patient sets foot in a hospital, he is already on an unequal footing,” said Elaine Hernandez, a sociologist at Indiana University.
The differences persist even though Black and Hispanic adults drastically altered their behavior. One study found that through the beginning of May, the average Black American practiced more social distancing than the average white American.
Officials in Chicago, Baltimore and other communities faced another threat: rumors flying about social media that Black people were somehow immune.
The top factor making people adopt self-protective behavior is personally knowing someone who fell ill, said Dr. Redbird. By the end of spring, Black and Hispanic Americans were 50 percent more likely than white Americans to know someone who had been sickened by the virus, her surveys found.
Dr. Hernandez, whose parents live in Arizona, said their neighbors who had not been scared in June had since changed their attitudes.
Her father, a physician, had set an example. Early on, he wore a mask with a silly mustache when he and his wife took walks, and they would decline friends’ invitations, saying, “No, we’re staying in our bubble.”
Now, she said, their neighbors are wearing masks, “and people are telling my father, ‘You were right,’” Dr. Hernandez said.
This Is the Beginning
There was no widespread agreement among experts about what is likely to happen in the years after the pandemic. Some scientists expected a quick economic recovery; others thought the damage could persist for years.
Working at home will become more common, some predicted, while crowded, open-plan offices may be changed. The just-in-time supply chains on which many businesses depend will need fixing because the processes failed to deliver adequate protective gear, ventilators and test materials.
A disease-modeling system like that used by the National Weather Service to predict storms is needed, said Caitlin Rivers, an epidemiologist at the Johns Hopkins Center for Health Security. Right now, the country has surveillance for seasonal flu but no national map tracking all disease outbreaks. As Dr. Thomas R. Frieden, a former C.D.C. director, recently pointed out, states are not even required to track the same data.
Several experts said they assumed that millions of Americans who have been left without health insurance or forced to line up at food banks would vote for politicians favoring universal health care, paid sick leave, greater income equality and other changes.
But given the country’s deep political divisions, no researcher was certain what the outcome of the coming election would be.
Dr. Redbird said her polling of Americans showed “little faith in institutions across the board — we’re not seeing an increase in trust in science or an appetite for universal health care or workers equity.”
The Trump administration did little to earn trust. More than six months into the worst health crisis in a century, Mr. Trump only last week urged Americans to wear masks and canceled the Republican convention in Florida, the kind of high-risk indoor event that states have been banning since mid-March.
“It will probably, unfortunately, get worse before it gets better,” Mr. Trump said at the first of the resurrected coronavirus task force briefings earlier this month, which included no scientists or health officials. The briefings were discontinued in April amid his rosy predications that the epidemic would soon be over.
Mr. Trump has ignored, contradicted or disparaged his scientific advisers, repeatedly saying that the virus simply would go away, touting unproven drugs like hydroxychloroquine even after they were shown to be ineffective and sometimes dangerous, and suggesting that disinfectants or lethal ultraviolet light might be used inside the body.
Millions of Americans have lost their jobs and their health insurance, and are in danger of losing their homes, even as they find themselves in the path of a lethal disease. The Trump presidency “is the symptom of the denigration of science and the gutting of the public contract about what we owe each other as citizens,” said Dr. Joia S. Mukherjee, the chief medical officer of Partners in Health in Boston.
One lesson that will surely be learned is that the country needs to be better prepared for microbial assaults, said Dr. Julie Gerberding, a former director of the C.D.C.
“This is not a once-in-a-century event. It’s a harbinger of things to come.”
Vaccines from the U.K., U.S. and China are sprinting ahead in a global race that involves at least 197 vaccine candidates and is producing geopolitical clashes even as it promises a possible pandemic escape route.
Driving the news: The first two candidates to reach phase three trials — one from the University of Oxford and AstraZeneca, the other from China — both appear safe and produce immune responses, according to preliminary results published today in The Lancet.
A vaccine from Moderna, the U.S. biotech firm, is heading into phase three trials after similarly encouraging initial results.
There are at least 16 other vaccines currently in clinical trials in Australia, France, Germany, India, Russia, South Korea, the U.K., the U.S. and China, which is experimenting with a variety of vaccine types and has five candidates already in trials.
What they’re saying: Experts are increasingly confident that it’s no longer a question of if but when vaccines will be available.
“Absolutely, for sure, we will get more than one vaccine,” Barry Bloom, a professor of public health at Harvard, told reporters today.
He cautioned that it’s not yet clear which vaccines will win the race and that we won’t know how effective they are in protecting against COVID-19 — and for how long — until after phase three trials.
Pressed on when a vaccine could be approved, Bloom said that while it seemed “utterly crazy seven months ago,” January was looking increasingly realistic.
Richard Horton, The Lancet‘s editor-in-chief, is more cautious: “If we have a vaccine by the end of 2021, we will have done incredibly well.”
Zeke Emanuel, chair of the Department of Medical Ethics and Health Policy at the University of Pennsylvania, splits the difference: “Seven months after we got the genome, to have three vaccines in phase three is literally unprecedented. If in six to eight months we get a license, that will be, again, totally unprecedented in world history.”
But, but, but: “Getting something approved doesn’t protect you from COVID,” Emanuel warns.
The challenges of producing, distributing and delivering a vaccine (particularly in two doses, as the Oxford vaccine requires) around the entire world are hard to even fathom.
Even distributing a vaccine in one country will require an unprecedented buildup of facilities, materials (like glass vials), personnel and protocols, assuming enough people are even willing to take it.
The global picture is even murkier. Several countries and pharmaceutical companies have committed to “fair and equitable” distribution.
In principle, that would suggest a vulnerable front-line worker in Uganda, say, should get the vaccine before a young, healthy person in the United States.
In practice, well … no one really knows.
The bottom line: “It’s very fragmented, and in some ways that’s understandable,” Horton says. “But the danger of that is that many countries will lose out and only the strongest country, the country with the most money, will win.”
If countries hoard supplies rather than prioritizing at-risk people elsewhere, Bloom says, “that should be a cause not just of global concern but of global shame.”
For now, governments are prioritizing their own populations.
The Trump administration is pouring at least $3.5 billion into the development and manufacture of three leading vaccine candidates, with the promise of hundreds of millions of doses should they prove safe and effective.
Even as the homegrown Oxford vaccine takes a global lead, the U.K. is hedging its bets by purchasing 90 million doses being developed by German and French companies.
The U.K. and U.S. have both also put in large pre-orders of the Oxford vaccine, though AstraZeneca says 1 billion doses will also be manufactured in India and distributed mainly to other low- and middle-income countries.
The WHO and EU are attempting to create a framework for distributing the vaccine globally, though the U.S. has declined to take part.
What to watch: Managing the largest vaccination project in history will clearly require global collaboration — but it’s also becoming a competition between rival powers.
“Six months from now, we will be in a situation where a few countries will have vaccines, and we believe those countries will be the UK, Russia, China and the US,” Kirill Dmitriev, the head of Russia’s sovereign wealth fund, told the FT.
Between the lines: Others are less certain Russia will be in that group, though Dmitriev says a vaccine bankrolled by his fund and developed by the state-run Gamaleya Institute will move into phase three trials next month.
“Basically other countries will decide, you know, which vaccine to buy … and who do you trust?”
— Kirill Dmitriev
State of play: There’s a clear lack of trust among the competitors.
According to the U.S, U.K. and Canada, hackers linked to Russian military intelligence have attempted to steal vaccine research in order to aid their own efforts.
The U.S. has also accused China of pilfering American research.