The new omicron variant is leading to an increase in breakthrough cases in vaccinated individuals, health experts said, but those who are boosted have the best chance at protection. The question remains, however, is one booster shot better than the others?
Public health experts say while fully vaccinated and boosted individuals are reporting an increase in cases, they continue to be milder infections than unvaccinated individuals.
Still, it's a question many ask as they prepare for their booster shots, with mixing and matching now authorized by U.S. regulators.
Here's what we know so far:
Does Pfizer's booster shot protect against omicron?
Pfizer said this month that a booster dose of its COVID-19 vaccine may offer important protection against the new omicron variant even though the initial two doses appear significantly less effective.
Pfizer and its partner BioNTech said that while two doses may not be protective enough to prevent infection, lab tests showed a booster increased by 25-fold people's levels of virus-fighting antibodies.
Blood samples taken a month after a booster showed people harbored levels of omicron-neutralizing antibodies that were similar to amounts proven protective against earlier variants after two doses.
Does Moderna's booster shot protect against omicron?
Moderna said its COVID-19 booster does appear to provide protection against the omicron variant.
In an announcement earlier this month, the drug company said preliminary data from lab testing found the version of its booster currently in use in the United States and elsewhere provided increased antibody levels to neutralize the virus. But it also found that a double dose of the booster shot provided a much greater increase in those levels.
The drug company said its currently FDA-approved 50 microgram booster was found to increase neutralizing antibody levels against omicron 37-fold compared to pre-boost levels. Meanwhile, it found that a 100 microgram booster dose gave an 83-fold increase in neutralizing antibody levels.
What about Johnson & Johnson?
Preliminary results from the Sisonke study, which have not been peer-reviewed, found that for people who had received one vaccine dose, the booster improved protection against hospitalization to 85 percent from 63 percent.
The study, carried out by the South African Medical Research Council compared 69,000 healthcare workers in South Africa to a group of unvaccinated South Africans.
The trial took place in November and December but participants were enrolled before the current wave now sweeping across the country, allowing researchers to "evaluate the effectiveness of the Company’s Covid-19 vaccine specifically as omicron became the dominant variant in the country," Johnson & Johnson said in a statement.
The Food and Drug Administration approved the Johnson & Johnson booster in October, but earlier this month the Centers for Disease Control and Prevention said people should get the Pfizer-BioNTech and Moderna boosters instead where possible, citing concerns over extremely rare blood clots.
Chicago's top doctor, Chicago Department of Public Health Commissioner Dr. Allison Arwady suggested those who got the J&J vaccine instead get a Moderna or Pfizer booster shot.
"It's especially important for people who got the J&J vaccine, if it's been just two months, please get a booster and have that booster be either Pfizer or Moderna," she said. "If you started with Pfizer or Moderna, your booster can be the same... but the most important thing is to get vaccinated and all three vaccines do remain available because we know that there are people who continue to prefer the J&J vaccine. I'm fine with that, just make sure you get a booster two months later."
Is one vaccine better than the others?
Overall, Arwady said data currently shows both the Pfizer and Moderna vaccines are performing better than Johnson & Johnson's vaccine at preventing breakthrough infections, but all three protect against hospitalization and death.
"The CDC has changed its guidance to recommend as the first choice either Pfizer or Moderna," Arwady said. "I want to reassure people that the J&J vaccine continues to do a good job of protecting against those severe illnesses, but we are seeing more breakthroughs."
In a small preliminary study out of South Africa, where the omicron variant was first detected, scientists said the variant significantly reduces antibody protection generated by Pfizer and BioNTech's vaccine, although people who have recovered from the virus and received a booster shot will likely have more protection from severe disease.
The findings of the study were first released earlier this month.
While breakthrough infections are seemingly on the rise across all vaccines, cases in fully vaccinated and boosted individuals appear to be milder compared to unvaccinated patients, experts said.
"Hospitals, for the most part, are seeing people seriously ill with COVID, especially the unvaccinated," Arwady said. "The symptoms that we're seeing are not different with omicron than they were with delta, than they weren't with the original. It's just that where we are seeing more of is what we call breakthrough infections. So the vaccines continue to protect, but not as well against infection although they continue to protect beautifully against severe illness."
In Chicago and multiple Midwestern states, early cases of the omicron variant appeared in fully vaccinated residents, some of whom also received booster doses, though symptoms have so far remained mild in those populations.
"If [fully vaccinated people] get COVID, as opposed to getting seriously ill and having fevers for days and difficulty breathing, etc., they may only experience it as a mild illness," Arwady said. "They may only feel like they have a cold. That's good because they're not getting seriously sick. They're not threatening the healthcare system, but it's certainly of some concern because they do have the potential to transmit to others."
The unvaccinated, however, are experiencing similar symptoms to early on in the pandemic, Arwady said.
"People who are unvaccinated present in the same way: fevers, cough, chills, shortness of breath," she said.
Arwady's comments echo those of other medical experts who are watching omicron cases.
In New York, where cases continue to surge, an ER doctor who became known on social media during the pandemic for his documentation of the battle against COVID, reported breakthrough cases he has seen in those with booster shots experienced "mild" symptoms.
"By mild I mean mostly sore throat. Lots of sore throat," Craig Spencer wrote on Twitter. "Also some fatigue, maybe some muscle pain. No difficulty breathing. No shortness of breath. All a little uncomfortable, but fine."
Cases in people who were fully vaccinated with either Pfizer or Moderna's vaccine, but not boosted, remained mild, but slightly more intense.
"More fatigued. More fever. More coughing. A little more miserable overall. But no shortness of breath. No difficulty breathing," he wrote.
For those with Johnson & Johnson who were not boosted, he wrote the patients "felt horrible," with fevers, fatigue, coughs and shortness of breath, but did not require hospitalization or oxygen.
In the unvaccinated, however, the symptoms were more severe.
"Almost every single patient that I’ve taken care of that needed to be admitted for Covid has been unvaccinated," Spencer wrote. "Every one with profound shortness of breath. Every one whose oxygen dropped when they walked. Every one needing oxygen to breath regularly."
But despite reports of milder infections among the vaccinated, in Illinois, hospitalizations have been rising.
Pediatric hospitalizations are also rising across several states in the U.S., including in Illinois, an NBC News analysis of Department of Health and Human Services data found.
"No vaccine is perfect, for one thing," said Dr. Egon Ozer, who works in infectious diseases at Northwestern Medicine. "No vaccine is going to be a magic bullet. So, especially with so much virus that’s still circulating, there’s always potential that there’s going to be some breakthrough, that people are still going to be able to get some degree of the virus. That’s certainly been the case with delta, as well.”
At the same time, people who contract a breakthrough infection after receiving the COVID-19 vaccine may acquire a "super immunity" to the virus, researchers from the Oregon Health & Science University found.
A study, which was published in the Journal of the American Medical Association, revealed antibodies in blood samples of those with breakthrough infections were as much as 1,000% times more effective than those generated two weeks following the second dose of the Pfizer vaccine.
As part of the study, blood samples were collected from 52 people, all university employees who received the Pfizer vaccine. A total of 26 people were identified as having mild breakthrough infections following vaccination. Of those cases, 10 involved the highly-contagious delta variant, nine were non-delta and seven were unknown variants, according to the study.