As the COVID-19 pandemic evolves, we answer 7 lingering vaccine questions

It’s now open season for COVID-19 vaccines across the United States.

After months of having to scramble to find a shot, the tables have turned and most people who want one can get one. Everyone 16 years and older is eligible for a vaccine, and the U.S. Food and Drug Administration on May 10 extended emergency use authorization for Pfizer’s jab to those aged 12 to 15 years old (SN: 5/10/21).

So far, nearly 60 percent of adults 18 years and older — or around 150 million people —  have gotten at least one dose as of May 10. President Joe Biden has set a goal of 70 percent of adults, or around 180 million, getting at least one dose by July 4, and 160 million adults being fully vaccinated — at least two weeks beyond their last shot — by that date.

But with supply beginning to outstrip demand in many parts of the country, that goal could be difficult to reach. Local officials already are launching innovative ways to reach people who are hesitant to get the shot, from going door-to-door to address people’s concerns to promising a free beer or baseball game ticket with each jab.

How many people get the shots will influence when life in the United States might approach something resembling a pre-pandemic normal. Computer simulations showed that if up to 75 percent of eligible people are on track to get vaccinated by September, there could be a sharp drop in cases of COVID-19 even earlier, by July, researchers report May 5 in Morbidity and Mortality Weekly Report. That decline may happen even as health officials loosen some public health guidelines, the simulations showed.

The U.S. Centers for Disease Control and Prevention has already revised mask-wearing recommendations for people who are fully vaccinated. And on May 9, Anthony Fauci, Biden’s top medical adviser for the pandemic, suggested during an interview on ABC’s “This Week” that as vaccinations rise and daily new cases drop, requirements for wearing masks indoors could ease. 

“We are not out of the woods yet,” CDC Director Rochelle Walensky said in a news conference on May 5. “But we could be very close.”

As we enter this new phase of the pandemic in the United States — amid a push to get doses to as many willing (or willing-to-be-convinced) people as possible — here are some of the big outstanding questions about vaccines.

How long does immunity last?

The short answer is that researchers don’t know yet. But studies suggest that for most people, antibodies that recognize the coronavirus can last at least a year after an infection — perhaps longer (SN: 11/24/20). And evidence is building that vaccines provide superior protection than natural infection, so it’s not unreasonable to expect that immunity might be longer-lasting for vaccinated people.

One small study, for instance, found that of 19 people tested for antibodies a year after getting sick with COVID-19, 17 people still had detectable levels, researchers report in a preliminary study posted May 2 at medRxiv.org. Those who had more severe COVID-19 symptoms were more likely to have higher antibody levels, the researchers found. So it’s possible that people who had mild infections may become susceptible to getting infected again sooner than severely ill individuals.

Data for how long the immune response sparked by a vaccine lasts is trickling in. People who received Moderna’s mRNA shot still have high levels of antibodies six months after getting the second dose, suggesting that they remain protected against COVID-19, researchers reported April 6 in the New England Journal of Medicine. And Pfizer’s jab, which uses a similar technology, has an efficacy of 91.3 percent against COVID-19 symptoms after six months, the pharmaceutical company announced in a news release on April 1.  

Also, the immune system has more in its arsenal than just antibodies. Immune cells called T cells are also important for fighting off infections. Studies hint that T cells also stick around for at least six months after recovery from a natural infection, and potentially for years to come.

If I didn’t have side effects after getting the vaccine, is it working? 

This is the most common question people ask Juliet Morrison, a virologist at the University of California, Riverside. “Everyone keeps saying, ‘I didn’t feel anything. Am I protected?’”

Morrison reassures her questioners with data. In Moderna’s 30,000-person trial, about 79 percent of people who got the vaccine had whole-body, or systemic, side effects, most commonly headache, fatigue and muscle aches. Some had chills or fever.  That left more than 20 percent of people who didn’t have bad side effects beyond an achy arm, or sometimes no side effects at all. But the vaccine’s efficacy was 94 percent. “That’s pretty compelling evidence that you do not need to have the adverse effects to develop immunity against SARS-CoV-2,” Morrison says.

About 37 percent of people in the placebo group in Moderna’s trial also reported systemic side effects. “That might suggest some people have adverse reactions just as a result of the process of receiving an injection, or they might have psyched themselves up about receiving the vaccine,” she says.

Many of the side effects are produced by immune responses that aren’t responsible for building lasting immunity, says Brianne Barker, an immunologist at Drew University in Madison, N.J. “Just because you’re not inducing the particular response that leads to fever, doesn’t mean you aren’t inducing the part that we’re hoping to induce with the vaccine.”

Should I get an antibody test to tell if the vaccine worked?

No. That’s not recommended because many of the antibody tests on the market now don’t test for antibodies like those made after getting vaccinated. Antibody tests usually test for antibodies against the virus’s nucleocapsid, or N protein. Some also test for antibodies against the coronavirus’ spike protein. Such tests are used to determine whether people have had SARS-CoV-2 infections in the past.

Since the vaccines contain only the spike protein, people who have been vaccinated but never had COVID-19 would not have antibodies directed against the N protein. They would get a negative result or indeterminate result from tests that detect N protein antibodies.

“You just need to trust that the efficacy of these vaccines is very high,” Morrison says.

If I have had COVID-19, do I need to be vaccinated?  

“All of the evidence says yes,” Barker says.  “The immune response you make when you’re infected with SARS-CoV-2 is not ideal.”

That’s because at least four of the coronavirus’s proteins inhibit immune responses and may damage the ability to make lasting immune memories. Studies also indicate that people who have gotten two doses of an mRNA vaccine make more neutralizing antibodies — the kind that help prevent the virus from entering cells — than people who have recovered from COVID-19.

“The immunity the vaccines confer is much more robust than the immunity from an infection,” Morrison says. “The vaccines that we have do a much better job than natural infection does.”

Scientists are still debating whether people who had previous infections need both doses of the mRNA vaccines or if they can get away with just one dose (SN: 3/3/21). For logistical reasons, health officials are currently advising that everyone get the recommended number of doses for the vaccine they’re given (two doses for the mRNA vaccines, one for Johnson & Johnson).

People who got sick and were treated with monoclonal antibodies or with convalescent plasma should wait 90 days before getting a COVID-19 vaccine, as these therapies can otherwise interfere with the immune response, says Matthew Laurens, a pediatric infectious diseases physician and vaccine researcher at the University of Maryland School of Medicine in Baltimore.

Can the vaccine help people recover from long COVID?

Some anecdotal and preliminary evidence suggests it might. About 30 percent to 40 percent of people who have persistent symptoms, known as post-acute sequelae of COVID (PASC), or long- COVID, say they feel better after vaccination.

Exactly why that is isn’t known. One hypothesis is that people with long-COVID never quite cleared the infection. Vaccination may help give any lingering virus the boot. Or it may give the immune system a reset.

Researchers are launching clinical trials to test whether vaccination really can help with the long-term symptoms. 

Can the current vaccines protect me from variants?

For the variants that have emerged so far, antibodies sparked by the COVID-19 vaccines used in the United States still seem to do their job and protect people from the worst of the disease. And the shots seem to provide superior protection against variants than previous infections do, Fauci said in a news conference on May 5.

Studies of Pfizer’s vaccine in Israel suggest it is highly effective against a variant first identified in the United Kingdom, called B.1.1.7 (SN: 4/19/21). In Qatar, Pfizer’s shot was 89.5 percent effective against COVID-19 symptoms for infections caused by that variant, researchers report May 5 in the New England Journal of Medicine. For a variant that was first identified in South Africa — called B.1.351 — the vaccine was 75 percent effective against symptomatic COVID-19, the team found. That’s heartening news because the variant has a mutation that helps the virus evade antibodies to infect lab-grown cells (SN: 1/27/21). The shot’s effectiveness to prevent severe disease or death caused by both variants was even higher, coming in at 97.4 percent.  

Other vaccines, including one developed by Novavax, are also showing some promise against variants (SN: 1/28/21). In South Africa where B.1.351 is prevalent, Novavax’s shot had an efficacy of 60 percent in participants without HIV, researchers report  May 5 in the New England Journal of Medicine. Johnson & Johnson’s jab had an efficacy of 64 percent against moderate to severe COVID-19in a South African trial. AstraZeneca’s vaccine, on the other hand, was only 10 percent effective against B.1.351 (SN: 3/22/21).   

Some vaccine developers are making moves to update their shots. Moderna, for example, announced May 5 that giving people a third dose boosted the immune response against variants first identified in South Africa and Brazil. Participants in the trial either received a third dose of the original vaccine or an adapted one based on the variant identified in South Africa. Those who got the adapted version had antibodies that were better at stopping the variant viruses from infecting cells compared with the antibodies from people who got a third dose of the original formulation.

Moderna is also testing a version that includes an equal mix of the original strain and the variant from South Africa.     

Is it possible to reach herd immunity?

In short, we still don’t know. But achieving herd immunity in the United States is seeming much harder as the pace of vaccinations slows and more contagious variants loom.

Long held up as the ultimate end of the pandemic, herd immunity is the proportion of a population that must be immune to prevent the virus from spreading. When the average infected person spreads the virus to less than one other person, herd immunity is reached and small outbreaks can’t balloon out of control.

Early on, estimates of the threshold needed to reach herd immunity estimates ranged from 60 percent to 70 percent of a population. That number stemmed from initial estimates of the contagiousness of the virus. But viruses can change, and estimates have ticked above 80 percent as more worrisome variants, like B.1.1.7, which is up to 70 percent more transmissible, gain steam (SN: 4/19/21). That variant is now the dominant one causing coronavirus infections in the United States.

It will take exceeding the theoretical threshold to reach herd immunity in the real world. That’s because vaccines aren’t 100 percent effective. And scientists still aren’t sure how well, or durably, they prevent someone from transmitting the virus, although there are tantalizing hints that vaccinated people who do get infected carry less virus and so are less infectious (SN: 2/12/21) . Even with a maximally effective vaccine, there may not be enough people willing to take it to reach herd immunity. According to recent polls, about 25 to 30 percent of Americans express reluctance to get the vaccine.

Biden’s goal of vaccinating 70 percent of adults with at least one shot by July 4 includes about 55 percent of the total population. That likely wouldn’t push us over the herd immunity threshold, but it would still help curb the pandemic. In Israel, for instance, about 60 percent of their population is now vaccinated and cases have dropped significantly and daily deaths have dropped to near zero in recent weeks.

“You vaccinate enough people, the infections are going to go down,” Fauci told the New York Times.