BY FRED GUTERL
The unprecedented swiftness with which medical science is developing a vaccine for COVID-19 is one of the most inspiring stories in this historic chapter. Vaccine candidates emerged only weeks after scientists identified SARS-CoV-2 and sequenced its genetic code. Universities and Big Pharma formed teams to develop vaccine candidates in short order. But just as quickly, the search for a vaccine became a political issue, and the sad result is that while the chances of an effective vaccine are rising, so is public distrust.
That's too bad, because the medical and scientific task of developing a COVID-19 vaccine is not the only critical ingredient to a successful vaccination campaign. Public buy-in is essential, because a vaccine is only effective when people agree to be inoculated. The political spectacle surrounding the vaccine efforts is undermining the public trust. Conflicting messages that seem likely to continue for the next two months of the presidential campaign will complicate efforts by doctors and public health officials in communicating, just as the threat of an autumn wave of infections approaches.
The race for a vaccine took shape early on. By July, Moderna, the Massachusetts drug company, moved the vaccine candidate that it was developing with nearly $1 billion dollars from the U.S. National Institutes of Health (NIH) into phase 3 clinical trials. Phase 3 is the gold standard in medicine, the final leg of testing a new vaccine has to complete before the Food and Drug Administration decides if its benefits are sufficiently large and its risks sufficiently small to justify releasing it to millions—perhaps billions—of otherwise healthy people. To persuade the FDA and the rest of the medical community, Moderna will enroll 30,000 people, give some of them the vaccine and the rest a placebo, and wait until 150 of them come down with COVID-19.
Russia's Gamaleya Research Institute wasn't far behind Moderna in the race to be first out with a vaccine. But in August, as Moderna was beginning the vast logistical operation of enrolling participants for its trial, Russia decided to authorize use of its vaccine even though it hadn't yet published the results of its phase 1 and 2 trials, which are used to gather data on toxicity and effectiveness from a small number of close-monitored participants. Russia was releasing a vaccine that had been tested on only 76 people.
Scientists denounced the move as "reckless," "foolish," "unethical" and potentially "disastrous." If the vaccine turned out to be unsafe or ineffective, it could undermine public trust in vaccines across the globe, at a time when persuading people to accept vaccination is important to containing COVID-19.
Undaunted by the example of Russia—or perhaps emboldened by it—President Trump earlier this month began suggesting that the U.S. might authorize its own vaccine before the election on November 3. "We remain on track to deliver a vaccine before the end of the year and maybe even before November 1st," he said at a news conference. "We think we can probably have it sometime during the month of October." He has repeated the claim.
Pushback came from many directions. Democratic candidates Joe Biden and Kamala Harris were quick to attack Trump for mixing politics and science. "I would not trust Donald Trump and it would have to be a credible source of information that talks about the efficacy and the reliability of whatever he's talking about," Harris told CNN. Scientists also objected. Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, said a vaccine before the end of the year was "not impossible" but "unlikely." Francis Collins, the director of the NIH, told Senators at a hearing that any decision to release a vaccine would be made on scientific grounds. "I just hope Americans will choose to take the information they need from scientists and not from politicians," he said.
Dr. Fauci Would Bet 10 Cents on Trump Having Vaccine by November, December
Even the pharmaceutical companies acted to head off any politically-timed vaccine authorization. Executives from nine drug companies, including Moderna, Pfizer and AstroZeneca, pledged to apply for government authorizations only "after demonstrating safety and efficacy through a Phase 3 clinical study." Two prominent NYU bioethicists, commenting on the sight of Big Pharma apparently defending the American public from a "politically-impaired" FDA, wrote in STAT, a health science news website, that "hell has frozen over." Dr. Fauci told Newsweek that a (hypothetical) presidential edict forcing the FDA to rush a vaccine would be "blown out of the water publicly by the people who understand what it takes to declare a vaccine safe and effective. It would be a public embarrassment."
The assurances have apparently not steadied a nervous public. According to a recent CBS poll, Americans are deeply worried about vaccine safety. The number of U.S. voters who say they would get a vaccine as soon as possible if one became available at no cost dropped to 21 percent, from 32 percent in late July. And two-thirds of voters would consider a vaccine announced this year to have been rushed for political rather than scientific purposes, and only 13 percent of those would get one. A new Kaiser Family Foundation poll found similar apprehension, with 62 percent expressing concern that political pressure would force the FDA to approve a vaccine without making sure it's safe and effective and the majority saying they would not get the shot, even if free, if the vaccine was approved before Election Day.
As if to underscore the risks, earlier this month AstraZeneca suspended phase-3 trials of the vaccine it has developed with Oxford University after a patient developed symptoms of a neurological disease (the trial has since resumed in the UK, but not yet in the U.S.).
Can you trust a coronavirus vaccine to be safe and effective when one is finally approved? Should you get the shot once a vaccine is approved in the U.S.? To help sort through all the uncertainty, we've put together the latest information on COVID-19 vaccines and the most frequently asked questions. Here's what we know so far—about the science, not the politics.
More than 100 COVID-19 vaccines are in trials.GETTYHow certain are we that a vaccine for COVID-19 will the forthcoming?
Fewer than one in five vaccine candidates typically survive the testing gauntlet, but at present there are more than 100 being tested for COVID-19. The chances that at least one of them will work is high. To date, nine vaccines are in phase 3 trials: Moderna's, which uses fragments of the coronavirus to stimulate an immune response; a similar vaccine by Pfizer, Biontech and Fosun Pharma; and the AstroZeneca-Oxford vaccine, which uses an adenovirus to carry coronavirus genes to cells, provoking an immune response. Trials of a vaccine called BCG, used in poor nations for tuberculosis and which may protect against COVID-19, are also underway.
A lot can still go wrong, however.
Clinical trials, for one, are notoriously hard to predict. Vaccines can look good in phase 1 and 2 only to fail in phase 3, where the sheer number of participants can reveal side-effects that smaller tests missed, while refining effectiveness rates. As happened with the drug hydroxychloroquine, a vaccine could turn out to confer benefits that do not outweigh harmful side effects, which means the treatment is worse than no treatment at all. Or it could simply fail to provide much protection against COVID-19. Failures, of course, are what the tests are designed to weed out.
It's important to keep in mind how quickly medical science is acting. Typically, it takes four or five years to develop a vaccine. It took Jonas Salk three years just to test the polio vaccine. That a vaccine for COVID-19 may come only a year after the virus was discovered is astonishing.
Still, there's no telling when ongoing trials will end. Scientists first have to collect enough data to be confident that they know what the risks and benefits are. Unlike, say, cancer drugs, where patients can often face an early death unless something is done to halt the progress of the disease, vaccines are given to millions of healthy people, which puts a premium on safety. Moderna, for instance, has enrolled about 22,000 people in its trial so far; the FDA requires data on 150 participants who fall ill with COVID-19. How quickly that happens depends on how prevalent the virus is in those areas where clinical trials are taking place—a trial might go more quickly in Arizona, where many people are infected, than in Maine, where infection rates are lower.
It also depends on how effective the vaccine is. A vaccine that protects 80 percent of the people who are inoculated would generate statistically significant results more slowly, because fewer people would get sick, than a trial that only protects half. For COVID-19, the FDA is aiming for 50 percent reduction in the disease, which effectively means it would accept anything above 30 percent. By comparison, the annual influenza vaccines are usually about 60 percent effective, which doesn't give iron-clad protection. However, Dr. Larry Corey of the Fred Hutchinson Cancer Research Center, an architect of the federal government's COVID-19 program, is hopeful that effectiveness will be "well north of 40 percent."
Stephen Hahn, commissioner of food and drugs at the U.S. Food and Drug Administration (FDA), drew criticism for exaggerating the promise of convalescent plasma as a COVID-19 treatment. He apologized.STEFANI REYNOLDS/BLOOMBERG/GETTYWhat happens if a weak vaccine is released?
Even a vaccine that leaves 40 or 50 percent of the people who are inoculated vulnerable to COVID-19 is better than no vaccine at all. And it would help in hastening herd immunity, which happens when enough people are immune to a virus to halt its spread.
The conventional wisdom is that herd immunity occurs when 70 percent of a population has immunity, though some statistical models suggest that 50 percent might be enough for COVID-19. That doesn't mean that a vaccine that protects 50-percent of those who are inoculated will be enough, because not everybody will take it—fewer than half of Americans plan to get a COVID-19 vaccine, according to an NBC poll, and one in three say they'd outright refuse to take one, according to Gallup. Public health officials worry that people may be discouraged to hear that a vaccine only works half the time and decide, why bother?
Most of the COVID-19 vaccines require two doses, which greatly complicates the logistics of the rollout because you need to manufacture and distribute twice as many shots. Another unknown is how durable these vaccines will be—how long will they last? Chances are on the order of months or years, but we don't know, and we may not know until after vaccines are released.
All this means that the discipline of wearing masks and social distancing and keeping restaurants partially filled is going to continue for the time being—probably a long time. "We should look at vaccines as part of the armamentarium we have against this virus," says Dr. Alan Bernstein, a member of Canada's coronavirus task force. "The other part is washing our hands, keeping distance and wearing a mask. Certainly, if I was immunized, I would still be doing these things."
What's the problem with releasing a vaccine early?
Release of a vaccine before there's enough data to know that the risk of harming people is much lower than the risk of helping them would violate public trust. "We can't have a vaccine released with great fanfare and then find out we have to pull the vaccine because it has an unacceptable risk of side-effects, because then the trust that the public has in the medical establishment—in the FDA and in vaccines in general—will be seriously damaged, perhaps permanently," says Richard Malley, a professor of pediatrics at Harvard Medical School. The reputations of U.S. medical institutions have already taken a hit after missteps on hydroxychloroquine, mask-wearing, convalescent plasma and COVID-19 tests. Another mistake on vaccines would only encourage anti-vaxxers, who in recent years have made it more difficult than it would otherwise be to protect people from measles, whooping cough and other diseases.
Early release of vaccines also complicates the task of studying other potential vaccines. Clinical trials require comparing a group of people who get the vaccine being tested with another group who get either a placebo or a standard vaccine. If an effective vaccine is already available, it's hard for scientists to enlist people willing to risk taking only a placebo for the sake of a new candidate that might or might not turn out to be better.
"There's urgency to develop a vaccine," says Malley, "but it doesn't mean you should rush and by-pass the usual criteria that have been established for decades to get to a vaccine that may not really be very efficacious."
When a vaccine comes out, how will we know it is safe?
Occasionally scientists will be ethically compelled to end a phase 3 trial early because data suggests that the drug, treatment or vaccine is overwhelmingly effective, which means they can't in good conscience continue withholding it from some test participants who may be receiving placebo instead. If a vaccine were released in this manner before Election Day, it would have gone through phase 1 and 2 trials, which focus on safety, and at least part way through phase 3 tests—but it would have to have done so well in phase 3 as to give scientists enough data to know unambiguously that the vaccine is safe and effective.
What would happen if the White House insisted on short-circuiting that process and releasing a vaccine without overwhelmingly positive data from phase 3 trials? I asked Dr. Corey, who has worked with Dr. Fauci to design Operation Warp Speed, the government's COVID-19 vaccine program. He pointed out that such a scenario would require the complicity of a great many scientists who have been collaborating on the nation's vaccine initiative. "We built these trials with incredible scientific expertise and review. There are hundreds of people who've seen the protocol. There are many layers of the review committees. The clinical trial sites involve the professors of infectious disease at essentially all our universities throughout the country and the people who have been on the front lines of taking care of people with COVID."
Has talk of an early release hurt the vaccine effort so far? "I can answer very emphatically that it hasn't," Corey says.
If the worst-case scenario comes to pass and the entire executive branch of the U.S. government—the FDA, the Centers for Disease Control, the Department of Health and Human Services—are compromised by political influence from the White House, we will have to rely on these scientists to speak out. So far, they have.
Is a vaccine our only hope?
Although vaccines are important for the long-term control of the coronavirus, there's also the possibility that drug companies will come out with treatments that make the disease less deadly. Imagine a drug that you could take at the onset of symptoms, or after you'd been exposed to someone who had COVID-19, that would eliminate the risk of being hospitalized or having long-lasting symptoms. For many people, that might turn COVID-19 from a terrifying disease to merely an unpleasant one.
Drug companies are working on oral or nasal treatments similar to remdesivir, the therapeutic that has shown some success earlier this year, which might be particularly effective when given early. So far drugs have shown promise in animal studies, says Malley. Drugs are much easier to test than vaccines, which require inoculating people and waiting for them to get sick. With a drug, you take already sick people, treat them and see if they improve. For this reason, Malley thinks early-stage drug therapies could be available in six months. "Obviously, taking pills whenever you're sick is not a long-term solution," he says. "But in a way, that may be more like to bring us relief from having to quarantine and avoid activities than a vaccine."
When will life return to normal?
"It's always dangerous to make these kinds of predictions, but I would say at a minimum, we're going to be doing this well into 2021," Dr. Fauci told Newsweek. "Getting into the summer and fall, I would predict that we're going to be approaching a certain degree of normality—not completely, because we're still going to have some coronavirus circulating around, but it's not going to be something that's a immobilizing society the way it currently is."
It's hard to wait that long.
When the coronavirus pandemic struck the Seattle area in February, Hilary Godwin, dean of the School of Public Health at the University of Washington, stopped visiting her elderly parents in Oregon. The train ride, which she used to love because she could read and sleep and look out the window, was now a potential virus-spreading event, and how could she justify risking her parents' health by staying in their guest room and eating in their kitchen? So, like millions of other people, she decided to put her family life on hold, hunker down and wait for a vaccine.
But as fall approaches, the prospect of having to give up congregating in backyards and sidewalk restaurants is enough to make a person consider coming out of the bunker. So Godwin drove with her husband and son for five-and-a-half hours to sit in her parents' backyard and talk from six feet away.
"It was the realization that it's not just three more months, or 10 more months. It's really that we're going to have learn to live with this new reality for another year or two, and that there's no point waiting. If I can come up with a way that may not be perfect, but at least is relatively safe, where I can spend time with them, I should do that now."
Correction: this story was updated to say that AstraZeneca's phase-3 trials of its COVID-19 vaccine have resumed in the U.K. but not yet in the U.S. -- 9/14/2020
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