By Sophie Putka

Some people may not know they are infected when they get boosted. Last week, our colleague at got her booster shot. She was ready for the vaccine's side effects -- fatigue, aches, maybe even a fever. What she didn't expect was a sickness that would last for days, and a positive rapid antigen test for COVID-19.

In retrospect, it made sense. She remembered a tickle in her throat the day of her booster shot, but she had just figured it was her body's response to a busy weekend. After deciding to get tested, she found out she'd been in contact with someone who had tested positive.

Thankfully, it appeared to be a mild infection. But what happens when someone gets a booster shot when they are already infected with SARS-CoV-2? We talked to infectious disease and microbiology experts to find out.

Whether you get inadvertently infected with the virus right before or right after getting boosted, an infection may cause symptoms, but isn't likely to interfere with the booster's effects, said Amesh Adalja, MD, an infectious disease physician at Johns Hopkins School of Public Health in Baltimore.

"I suspect it's not going to be a major effect other than that you might be contending with more symptoms from the vaccine and from the infection that you have at the same time," he said. "It could be more unpleasant than normal."

In fact, your chances of getting infected with SARS-CoV-2 are almost as high up to 6 days after getting a booster shot as with no booster. "If you only got your booster a day ago, then you might as well not have it at all," said Benjamin tenOever, PhD, a professor in the microbiology department at NYU Grossman School of Medicine.

When going in for a booster shot, vaccination site staff may ask if you're feeling symptoms of COVID-19. This isn't because the infection and the booster interact, but rather to protect everyone at the vaccination site. However, Simone Wildes, MD, an infectious disease physician at South Shore Health in South Weymouth, Massachusetts, said that while an infection close to or around the time of vaccination isn't uncommon or particularly harmful, it makes more sense to wait until antibody levels fall after an infection, and then get a booster.

The CDC initially recommended waiting 90 days after an infection to get vaccinated. But guidelines have since changed to reduce the chances that someone might skip the vaccine or booster altogether after waiting, she said. According to the updated guidelines, "People with COVID-19 who have symptoms should wait to be vaccinated until they have recovered from their illness and have met the criteria for discontinuing isolation."

Despite both the infection and vaccine potentially leading to symptoms that occur in response to a virus, the immune response to a vaccine, including the booster, and the immune response to the virus itself are different processes.

Immune Response to mRNA Vaccines

After receiving a first inoculation, a few cells in the body will pick up the injected mRNA, and begin to run what tenOever compared to a software program to produce the spike glycoprotein characterizing SARS-CoV-2. Antigen-presenting cells "are going to see this very strange-looking structure on the surface of muscle cells in your shoulder and they're going to manage a response to it, and that response takes some time," he said.

In those 2 to 3 weeks in which the immune response post-vaccine grows stronger, "antigen-presenting cells will teach your immune system how to recognize this foreign protein, which in this case, is spike," he added.

The mRNA that went into your arm also teaches the immune system to recognize the foreign spike protein in muscle cells, via immunoglobulin G -- but not in the mucosa, where it would use immunoglobulin A. Without this mucosal immunity, tenOever explained, SARS-CoV-2 can infect the upper respiratory system after exposure to the virus, but for the most part, can't get any further in a vaccinated person.

Immune Response to SARS-CoV-2

If you are infected right around the time of the booster, not only are you missing mucosal immunity, but you also lack the advantage of the learning process the immune cells undergo in the weeks following vaccination. "The longer the time between your booster and seeing an actual virus, the better off you are, because you've given your immune system that much more time to explore different spaces and ways to stop the virus," tenOever said.

But if you do happen to get an infection and recover, the immune learning process is refined in a way that the mRNA vaccine can't induce. "When you get infected, what happens is the virus obviously now starts killing cells and destroying cells and making a giant mess and losing lots of inflammation. But it also allows your immune system to recognize other components," he noted, such as nucleocapsid protein, which is inside the virus, unlike the spike proteins.

How to Tell the Difference Between the Two

Adalja said that though fever, muscle aches and pains, and headaches can come with both immune response scenarios, vaccine side effects are distinguishable from the symptoms of a breakthrough infection -- to an extent.

"Upper respiratory symptoms would be one clue," Adalja explained. These include a sore throat, congestion, and the loss of taste and smell.

"And then the other aspect would be if it's prolonged," he added. While side effects from the booster may only last a day or two, a long stretch of illness likely means an infection.

"That's the key thing," said Wildes. "If you're having the symptoms for more than 72 hours, then we strongly recommend that you reach out to your healthcare provider and get tested, because it shouldn't be going beyond that point with the vaccine for most people."

Hybrid Immunity

Because the body builds such a robust response system after infection, immunity from infection can be highly protective -- but is even more so with vaccination. In a study, researchers found that vaccinated people with previous infection better neutralized SARS-CoV-2 than did their vaccinated counterparts with no previous infection. A preprint study out of Israel suggested that hybrid immunity may last longer than vaccine-induced immunity, but both decline over time.

So, how long does hybrid immunity fend off reinfection? "If [natural immunity] happened with a Delta variant, it may not be sufficient against the Omicron variant. But then again, the booster might not be sufficient against it either," said Adalja. "So, I think that's an open question."

If it was the case that you got enough immunity from a natural infection alone, then we wouldn't be advocating for vaccines in these individuals as well, noted Wildes. "It's not well sorted out because what happens is, different people develop different levels of antibodies."

What to Expect

In any case, an infection that occurs before a booster shot has time to build up the body's full defenses would likely be mild. This, of course, depends on other factors: age, comorbidities, and immunocompromised status. It is still possible to get a serious illness, and to spread the virus to others, experts said.

The bottom line is developing a breakthrough infection right before or right after a booster shot is possible, and the resulting hybrid immunity confers some extra protection. And, as with all responses to the virus, it varies from person to person.

But the most important thing, experts emphasized, is to get vaccinated in the first place, and to get a booster when appropriate.

"Just get your booster," said Wildes. "I want to make sure that the word gets out that the data are clear: the two-dose vaccine is not going to be effective against the Omicron variant, which is already here."