The FDA has authorized Pfizer’s COVID-19 vaccine. Now what?

The FDA has authorized Pfizer’s COVID-19 vaccine. Now what?

December 15, 2020 Off By Carolyn Gramling

It’s the first to win emergency use approval in the United States

Millions of Americans will soon be lining up for COVID-19 shots.

On December 11, the Food and Drug Administration granted emergency use authorization for the Pfizer-BioNTech vaccine for those age 16 and older. The decision comes as numbers of COVID-19 cases, hospitalizations and deaths have been rising at alarming rates. The United States recorded a record-high 3,411 COVID-19 deaths on December 9.

The United States is the latest country to authorize the vaccine, after the United Kingdom, Canada, Bahrain and Saudi Arabia (SN: 12/2/20).

Here’s what happens next in the United States.
The vaccine starts to be shipped, but won’t have a widespread impact for several months.

The Pfizer-BioNTech vaccine will likely be an enormous help in immediately keeping some people out of hospitals and preventing deaths.

But while the vaccine and any others that are authorized may protect individual people, when it comes to widespread public health changes, “it will likely be several months before we get the full positive impact of a vaccine,” infectious diseases expert Anthony Fauci said December 11 in an online interview with JAMA.

Initial doses of vaccines will be limited. The federal government had previously said that 6.4 million Pfizer doses would be shipped out to states within 24 hours of FDA’s authorization. On December 9, a top official with the Trump Administration’s Operation Warp Speed said that only about half of those doses, about 2.9 million, will be shipped within 24 hours of emergency use authorization. Another 2.9 million will be held for distribution until the first vaccinated people are due for their second shot 21 days later. Another half a million doses have been set aside in a reserve, U.S. Army Gen. Gustave Perna, who is Warp Speed’s chief operating officer, said in a news conference. Vaccinations could begin as soon as early next week.

A similar vaccine made by biotechnology company Moderna will undergo review by an advisory committee to FDA on December 17. An initial 12.5 million doses of that vaccine are expected to ship if it is authorized.

Overall, “we believe that there will be enough vaccine available for 20 million first vaccinations in the month of December,” said Alex Azar, the secretary of Health and Human Services, said in the Dec. 9 news conference.

A Centers for Disease Control and Prevention advisory panel has recommended that health care workers and people living in nursing homes should be the first to get the vaccines, if both are authorized (SN: 12/1/20). But it will be up to states to work out the details of exactly who gets it and when.
Scientists will look for hidden side effects and other health issues.

As those doses are injected into arms, scientists will be on the lookout for answers to key questions. One big one: Are there hidden side effects?

In the United Kingdom, two people have had serious allergic reactions after getting Pfizer’s vaccine since its rollout December 8, prompting health officials there to recommend that people with “significant allergies” that trigger anaphylaxis not take the vaccine.

Those allergic reactions raise questions about whether the vaccine might cause very rare side effects not seen in the clinical trials. The trials, which included more than 40,000 people, found that the vaccine is safe, with side effects that include fever, chills, headache, pain at the injection site and fatigue. Those side effects tended to last for only a day or two and were generally mild to moderate.

Although such side effects could be unpleasant for some people, they are common reactions to vaccines approved for other diseases, experts say. But some side effects may come to light only once millions instead of thousands of people have been vaccinated.

And as millions of people get vaccinated, many other health issues, including deaths, may arise that may not be related to the vaccine but could be difficult to separate out, says Marm Kilpatrick, an infectious diseases researcher at the University of California, Santa Cruz.

Six people died during the clinical trials, though only two were in the vaccine group. Their deaths — of a heart attack and of preexisting narrowing of blood vessels — were almost certainly not related to the vaccine, Kilpatrick says, but as many people get vaccinated, more deaths will happen just by chance, particularly among people with health problems. “Distinguishing the cause of all their deaths from any vaccinated related effects will not be trivial,” he says.
People who already had COVID-19 may need to be vaccinated, too.

A small number of people in the Pfizer trial had antibodies in their blood indicating that they had been infected prior to joining the study. Some of those people went on to develop COVID-19 during the study. That may suggest that having the disease doesn’t completely protect people from reinfection and that people who previously had COVID-19 should also get vaccinated.

But Kilpatrick, of University of California, Santa Cruz, isn’t convinced. “I wouldn’t say these data are slam dunk evidence that prior infection provides no protection,” he says. It’s important to know when those people had COVID-19, he says. Some people can continue to produce viral RNA for long periods of time, so some of the RNA detected might not be from a true reinfection, but left over from the first bout of disease.

To determine whether there is reinfection, doctors would need to determine the genetic makeup of the virus causing the first round of illness and compare it with the virus causing later rounds, such has been done for a few confirmed cases of reinfections (SN: 8/24/20).

Also unknown is whether previously infected people could get away with a single vaccine shot to boost their natural immunity, or if they will need two shots like everyone else, says Mark Slifka, a microbiologist and immunologist at Oregon Health & Science University in Portland.
Scientists will wrestle with whether to vaccinate people in the placebo group.

Another giant question is how long vaccine-induced protection against the coronavirus lasts. Researchers could learn that over time by continuing to track cases arising in the placebo group and the vaccine group. But that raises a big question, too: Should people in the placebo group be given access to the vaccine? Pfizer has proposed to vaccinate the placebo group, but some scientists argue doing so would make it impossible to learn about the duration of protection and any long-term side effects.

People in the trial could ask to know whether they got the vaccine or not and ask for the vaccine if they were in the placebo group, but Slifka hopes the trial participants will continue to maintain their ignorance of which group they are in. Knowing could change the participant’s behavior and taint any data coming out of the trial, he says.

Many participants’ altruism will probably lead them to continue the trial as is. “The people who are on these studies are heroes,” Slifka says. “They’ve stepped up and stuck out their arms to get an experimental vaccine, not for just for themselves, but for the country and the world.”

But it becomes a trickier question about what to do about future vaccine trials. When vaccines are approved, it becomes unethical to do placebo-controlled trials. Instead, companies must show that their vaccines trigger immune reactions at least as strong as an existing vaccine.

Usually that is done by measuring levels of antibodies produced after vaccination. If a new vaccine meets a certain standard level known to be protective — called a correlate of immunity — then it might also be approved, provided it is safe. But no one knows what level of antibodies or other defenses are needed to protect against COVID-19.

Also, the Pfizer vaccine is not yet fully approved and is in limited quantities, so other companies may still need to compare their vaccines to placebos to determine whether they work. It could be difficult to recruit people to take part in such trials once more vaccines are authorized.
Research will continue on whether the vaccine works for children and other groups.

While the trials have found the Pfizer-BioNTech vaccine to be 95 percent effective overall, there’s not enough data to show that’s true for all populations.

Take children: Pfizer has been testing its vaccine in adolescents 12 and older and Moderna began testing its vaccine in adolescents December 10. There’s not yet enough data to say how well the vaccine works for them.

No companies have tested COVID-19 vaccines in kids younger than 12. Kids tend to develop milder symptoms of COVID-19 than adults do. As a result, trials testing effectiveness would have to be enormous if done the same way for children as in adults. Instead, vaccine makers might measure antibodies in younger vaccinated children to see whether kids have the same kinds of immune reactions to the vaccine as adults and teens.

There is also limited data on how well the Pfizer-BioNTech vaccine works in people with HIV or hepatitis B or hepatitis C or in other immune-compromised people.

“If you have a person who is on chemotherapy for a cancer or for an autoimmune disease, the likelihood … is that their level of response to any vaccine will not be as robust as someone who doesn’t have an underlying condition,” Fauci said December 11. “That doesn’t mean you don’t want to vaccinate them. That means you have to vaccinate them. But you’ve got to be prepared that you’re not going to have, necessarily, a 95 percent protection.”

There was a fear that any COVID-19 vaccines wouldn’t work well for older or obese people, because age and obesity can both diminish immune responses, and people in both groups are at increased risk of developing severe COVID-19 or dying (SN: 4/22/20). But data from the Pfizer trials suggest that the vaccine works just as well in people 65 and older as it does in younger adults. Obese people were also protected at levels similar to non-obese people. Scientists will want to confirm that these groups are actually protected by the vaccine.
Pfizer-BioNTech will continue to seek full FDA approval of its vaccine.

The company probably will need to collect additional safety, as well as effectiveness, data to win full approval from the FDA and other regulatory agencies around the world. Emergency use authorization is provisional and lasts only as long as the emergency continues, Peggy Hamburg, a former FDA commissioner explained during a news conference December 3 hosted by SciLine, an independent, free service for journalists based at the American Association for the Advancement of Science.

Full approval would mean the vaccine meets all safety and effectiveness standards and is no longer experimental. The vaccine would become the standard by which any new COVID-19 vaccine is judged.

Vaccine developers are also not allowed to market their product under emergency use provisions as they can when the product gains full FDA approval.
Life, slowly, returns to some semblance of normal?

Even with multiple vaccines, life may not return to pre-pandemic normal anytime soon. “My optimistic hope is that we’ll be getting back to more normal life by fall” next year, says Ross McKinney Jr., a pediatric infectious diseases specialist and chief science officer of the Association of American Medical Colleges, based in Washington, D.C.

Controlling the pandemic with mask wearing, social distancing, avoiding gatherings especially indoors and taking other safety measures will be key to “coming out the other side,” says Jason Schwartz, a vaccination policy researcher at Yale School of Public Health. “Vaccines are amazing,” he says, but, “they can’t work miracles.”