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BA.2, boosters, and the future of COVID-19 vaccination

Gabrielle Redford, Managing Editor
April 28, 2022

Even as the BA.2 omicron subvariant spreads rapidly across the country, hospitalizations and deaths remain low. Here’s what you need to know as the United States enters a new phase of the pandemic.

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If there’s one point on which all the experts agree, it is this: The spring surge of COVID-19 in the United States, caused by the hyper-contagious BA.2 omicron subvariant, will be unlike any other phase of the pandemic thus far.

In just the last two weeks, infections have increased by more than 50%, according to the New York TimesCOVID data tracker, but hospitalizations due to COVID-19 have risen only slightly and daily deaths are at their lowest level since the pandemic began.

“This surge feels qualitatively and quantitatively different from earlier surges in terms of the severity of disease and the mortality,” says Megan Ranney, MD, MPH, an emergency medicine physician and academic dean of the School of Public Health at Brown University in Rhode Island. “That is likely due to a combination of vaccines and boosters along with the fact that so many people were infected with the original omicron variant quite recently.”

Yet, the United States — and indeed, the global community — is still in the grips of a pandemic that continues to pose substantial risks for those who are unvaccinated, the elderly, the immunocompromised, and those with certain medical conditions, such as obesity and diabetes.

AAMCNews recently spoke with several of the foremost academic experts on COVID-19 for their advice on how best to navigate this next phase of the pandemic.

How concerned should we be about BA.2?

While BA.2 seems to lead to less severe disease, it is not, in fact, benign — especially for those who have not been vaccinated, or for those who were vaccinated but did not receive a booster shot.

“If you haven’t been vaccinated and boosted, and certainly if you’re over 50 or 60, or if you have some other significant medical issues, you should be very concerned,” says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, California. “If you’re fully vaccinated, including a booster, you should be pretty confident that you’re not going to get very sick if you do get an infection.”

But not getting very sick can still translate into flu-like symptoms — including fever, body aches, sore throat, congestion, and fatigue — for one or two weeks. And for a small subset of people — Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, puts it at 10% to 20% in unvaccinated patients and about half that in vaccinated patients — a COVID-19 infection can lead to long COVID. This is a constellation of symptoms, including extreme fatigue, brain fog, and trouble breathing, that can persist for months to years.

“[Plus], there has been a fair amount of research in the last six weeks about a bunch of bad outcomes a year out from a case of COVID that include heart attacks, strokes, blood clots, diabetes, and brain shrinkage,” he says. The risks were higher for those hospitalized for COVID-19 but were present even in some who had a mild case of the disease.

How protected are you with vaccination and a booster shot?

Vaccination and a booster shot provide good protection against severe disease, studies show. Two large studies published in JAMA in January 2022 showed that three doses of an mRNA vaccine were 90% to 95% protective against severe disease or death from both the omicron and delta variants.

Anna Durbin, MD, an infectious disease physician at Johns Hopkins University School of Medicine in Baltimore, says that the first booster shot is particularly important in teaching the immune system to recognize and respond to the coronavirus. “It’s important to understand that when these vaccines rolled out, we were at the height of a pandemic. We wanted vaccines quickly and safely and that is what drove the primary immunization series to be two shots, three or four weeks apart. But any immunologist will tell you that’s not the optimal timing for a two-shot regimen. We would have preferred to spread that out to two to three months apart, but that would have delayed authorization of the vaccines even further.”

Instead, a third shot was needed several months after the first shots. “By then, your immune system had calmed down from the original shots, and it was ready to rev up again,” she says.

While protection against severe disease remains robust after three shots, protection against infection wanes substantially over time, in part because each new variant of virus contains more mutations that make it both more transmissible and better able to evade the body’s immune response. The BA.1 strain of omicron carries more than 50 mutations from the original coronavirus strain that originated in Wuhan, China, while the BA.2 strain contains an additional eight mutations that seem to make it about 30% more transmissible than BA.1.

“About every couple of weeks, we learn that omicron has gotten a little bit smarter about how to infect people,” Wachter says.

Who should get a second booster – and when?

Because of mounting evidence of waning immunity after a first booster shot, the Food and Drug Administration in March authorized a second booster for anyone over 50 and for immunocompromised individuals who are at least four months past a first booster shot.

One study from Israel found that a fourth shot of the Pfizer-BioNTech COVID-19 vaccine provided protection against infection with omicron among adults 60 and over, but that protection waned quickly – peaking at 4 weeks and almost disappearing by 8 weeks post-shot.

The short-lived immunity from a second booster, combined with evidence that the first booster continues to provide protection against severe disease, has led to disagreement among experts, some of whom believe that second boosters are of limited value for most individuals.

“With these vaccines and with all vaccines for respiratory viruses, to be honest, our goal is not to prevent infection,” Durbin says. “Until I see rising cases and evidence of more severe disease, I would not recommend a [second] booster right now for most people.” Durbin does hope to see a reformulated vaccine developed in time for a fall booster campaign.

Topol believes if you’re eligible for a second booster, you should get one, citing three studies that show that a second booster is safe and provides greater protection against severe illness and death in those over 50.

“I think it’s a real mistake to be discounting the importance of [second] boosters,” he says. “Sure, if you’re living in a cave, you don’t need to worry. But if you’re traveling and mixing with people, and you’re in an area where cases are rising, then I think it would be good to get a booster.”

Wachter says that people over 60 with a high risk of a bad outcome from COVID-19 should definitely get the second booster. But younger individuals in lower risk groups have a more difficult decision to make.

“The facts about the second booster that people need to understand to make that choice are that first, your immunity after that first booster wanes considerably four to six months out. That’s unquestionable. The second booster raises your immunity about to the point where you were after the first booster. … Where it gets complicated is the length of protection. Do the benefits of getting the shot now outweigh the risks?”

One risk is that in a month or two, just when your immunity from a second booster is waning, the United States experiences a huge surge in cases — or you decide to travel or attend a large gathering. In that case, you will have squandered your immune boost just when you need it most.

“It’s like a coupon,” Topol says. “Do you want to use it now or save it for later?”

Durbin fears that those who wait too long to get a second booster would have to wait to get a reformulated vaccine in the fall. “My great hope is that in the fall, we’ll have a vaccine that’s different from the one we’ve had.”

There is some good news for those who are vaccinated and boosted —who also had a breakthrough omicron infection, though. “They do not need [a second booster],” Durbin says. “They have a little bit of an edge because they were infected.”

Indeed, while reinfection with BA.2 after a BA.1 infection is possible, it is rare and occurs mainly in unvaccinated individuals, according to a small Danish study.

How can individuals assess their own risk?

Wachter acknowledges that the temptation to throw up one’s hands at this stage of the pandemic is real. “I do this for a living and it’s confusing to me,” he says. Many of his 263,000 Twitter followers have said: “You tell me what you’re doing. I’ll do that.”

Wachter is fully vaccinated and received his second booster about two weeks ago. He is wearing an N95 mask or the equivalent in crowded indoor spaces and whenever he’s around people whose vaccination status or current symptoms he does not know, such as at the grocery store or on an airplane. “I would feel kind of bad if I got COVID in a place where I really could have kept myself protected,” he says. But he is going out to dinner with friends and having friends over to his home.

Ranney says the value of a high-quality mask cannot be understated. “This is the moment where you should expect that if you’re out and about, doing indoor activities, going to restaurants and concerts without a high-quality, good-fitting mask, you should expect that if you didn’t have omicron in the first wave, that you’re going to catch COVID,” she says. “[BA.2] is that contagious.”

Her lab has developed a COVID-19 risk calculator — MyCOVIDRisk.app — that can help you determine your risk of catching COVID-19. You enter your planned activity, how many vaccines you’ve gotten, your location, whether the activity is indoors or outdoors, and other factors — and the app spits out your risk of catching the disease. It also gives you options to change that risk.

“If you’re choosing to be out and about without a mask on, there is risk,” Ranney says. “You just need to be aware so you can make an informed choice." 

What is the future of vaccination?

Regardless of whether you receive a second booster or not now, there will likely be another booster shot in the fall.

Durbin predicts that we’ll have a bivalent vaccine — a vaccine that is designed to fight at least two strains of the coronavirus. Moderna recently announced that its bivalent vaccine containing strains of the beta and original coronaviruses performed better than its existing vaccine.

Ranney also believes we’ll have a bivalent vaccine but is hopeful that the fall booster incorporates some elements of the omicron strain. “It’s going to be too early for some of the exciting types of vaccine, like the nasal vaccines,” she says. “But I would suspect that what we’re going to get in the fall is tailored to the strains that we’re seeing. There is a possibility that there will be a combined COVID-flu vaccine, but that’s still up in the air.”

One concern among all the experts is booster fatigue — particularly if there are diminishing returns for subsequent booster shots.

“With each new booster, we’re losing more and more people,” Wachter says. “I’m not confident that if there’s a surge coming and there’s a campaign that says there’s a new vaccine that that will lead to a massive uptake.”

The use of antivirals and other therapeutics to counter the worst effects of COVID-19 will also be critical, Topol says.

The White House announced this week that it was doubling the number of pharmacies and clinics that would carry Paxlovid, an antiviral pill that has been shown to reduce the risk of hospitalization and death in infected people by almost 90%.

“We have to have complementary strategies,” Topol says. “We can’t keep going into the booster mode; it’s not an ideal way to counter a virus.”

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