As we get closer to a COVID-19 vaccine, it's exciting to imagine a day when the virus is gone. But a vaccine will not be a magic bullet. In fact, it may be only about 50% effective.
Dr. Anthony Fauci, chief of the National Institute of Health and Infectious Disease, has tried to set realistic expectations when discussing the importance of a vaccine. "We don't know yet what the efficacy might be. We don't know if it will be 50% or 60%," Fauci said during a Brown University event in August.
"I'd like it to be 75% or more," Fauci said, but he acknowledged that may not be realistic.
The Food and Drug Administration has said that once a vaccine is shown to be safe and at least 50% effective, it could be approved for use in the U.S.
So what does 50% efficacy mean?
"When we talk 'vaccine effectiveness,' what we're talking about is, 'How effective was the vaccine at preventing actual disease?' " explains scientist L.J. Tan, chief strategist of the nonprofit Immunization Action Coalition.
In other words, Tan says, "If you vaccinate 100 people, 50 people will not get disease."
This may not sound like an impressive rate of infection prevention, but there are other potential benefits to individuals and the community from getting vaccinated.
"It's possible that the [COVID-19] vaccine will reduce the severity of disease" in the other 50% who do get sick, says physician Bill Miller of The Ohio State University College of Public Health. "It may mean that people are less likely to be hospitalized, require ICU care or die."
"That's certainly the case with the influenza vaccine," Miller adds. "People who get the vaccine may still get the flu, but, for the most part, their disease is milder than if they hadn't had the vaccine."
Michael Ison, an infectious disease physician at Northwestern University Feinberg School of Medicine, echoes that sentiment. While it's true that 50 out of 100 people who get the vaccine could still end up getting infected with the coronavirus, "hopefully, the majority will have milder disease," Ison says. But he cautions there's a lot to learn in that regard, given that the studies of COVID-19 vaccine candidates are still very much underway.
"We really need to get some information from the trials that are ongoing to best understand what the impact will be," he says. Ison is a member of the research team at Northwestern that is conducting studies on COVID-19 and on influenza vaccines.
And here's the next reality check: The extent to which any vaccine that emerges will help halt the COVID-19 pandemic depends on how many people get the immunization.
In order to put this pandemic in the rearview mirror, a large percentage of the population needs to either be vaccinated or gain immunity via an infection with the virus (a much riskier route that would include many more deaths).
When a large portion of the population has immunity to the virus because of this sort of "herd immunity," it's unlikely to keep spreading. Even people who haven't been vaccinated (such as very young babies and those with compromised immune systems) are protected once this level of immunity in a population is achieved, because the illness has little opportunity to spread within the community — most people who run into the virus in this scenario are immune.
For the coronavirus, Ison says, " 'herd immunity' is seen when we have somewhere between 60% to 70% of the population having some degree of protection."
So — here's a little math — if 20% of the U.S. population ends up getting exposed to the virus and developing an infection before we have a vaccine (as is estimated to be the level of immunity in the New York City metro area right now), then we would still need an additional 40% of the population to gain protection via a vaccine.
And in order to get 40% of a population immune through vaccination — if you have a vaccine with 50% efficacy — "you're going to have to vaccinate 80% of the population," says Carlos del Rio, an infectious disease expert at Emory University. "So it's not going to happen right away."
For starters, Michael Ison says, there are logistical challenges to getting everyone vaccinated, given the mammoth undertaking of manufacturing and distributing a vaccine.
"It's going to take us months to get the entire population vaccinated if they are willing to get vaccinated," he says — which is another big "if." An NPR/PBS/Marist poll in August found that more than a third of Americans — 35% — say they won't get vaccinated when a vaccine comes available.
What's more, most of the candidate vaccines now being tested would require two separate doses to trigger their most effective protection, Ison says. So at a minimum, he notes, you've got a full month between the two doses of vaccine and a short period of time after the second dose before someone who was been vaccinated would be protected.
It's also still not known how long the immunity gained through any of the current COVID-19 vaccine candidates will last or to what extent the virus might mutate or change in a way that makes that vaccine less effective.
"What we will only know once we have the vaccine [approved and rolled out] is how effective it is, how long lasting the protection is and how much pressure it applies to the virus to change, to escape the pressures of the vaccine," Ison says.
Despite all these remaining unknowns, it is safe to say that any such vaccine against the coronavirus could play a significant role in reducing the spread of the virus.
"If a vaccine is 50% effective, that's still good," Miller says. That means that you have a good possibility of being protected. He says we should think about its effectiveness the way we do about the benefits of cancer treatments, for example.
"In some severe cancers, we'd be pretty happy to get a drug that gets us to 50% effectiveness," he notes.
Why do we need to test a proposed vaccine in so many people?
For now, it's important to see the experimental trials of each vaccine candidate through to the end, Miller says. The phase 3 trials will tell us a lot about the safety of a vaccine as well as its effectiveness.
The large studies now underway are being conducted as double-blind, placebo-controlled trials, which is considered the gold standard in scientific research. This means half the participants get the real vaccine and "half the patients get a placebo — a water shot," Ison says. And nobody — not the researchers nor the participants — will know until after the study is complete who got the placebo and who got the real vaccine.
"What we would like to see is that there's a difference in the rate of COVID-19 — with a much lower rate in patients who get the vaccine than in the patients who get the placebo," Ison says. But it takes time and a lot of people to see that sort of effect and to answer questions about safety.
The vaccine makers are aiming to enroll about 30,000 people in each trial.
"Side effects of vaccines [can be] very rare, so you need a lot of people to see if the vaccine causes any unexpected problems," Bill Miller explains. "These side effects must also be monitored carefully post-marketing to ensure that every important problem is identified."
Ison notes that there's another benefit to a large study — it helps researchers know how strong the immune response to a vaccine needs to be to be protective.
Will the vaccine protect older people? And what if I'm heavy?
With age, the immune system often mounts a lesser response to vaccination; that's why, for example, adults 65 and older can opt for a high-dose flu shot — that's thought to help bolster their protection. And scientists also know from prior research that the flu vaccine is less effective in people who carry a lot of extra weight. Ison says it's too soon to know if obesity or age will be a factor in the immune response to the COVID-19 vaccine candidates now being considered for use.
In research results so far, he says, "the small, phase 1 data shows that you can generate antibody responses even in older adults, but it'll be these larger studies that will tell us [whether] we need to use higher doses or more doses of the vaccine in certain cases." Results from phase 3 trials of safety and effectiveness are expected in the coming months.