It’s been dubbed a pandemic of the unvaccinated by federal officials. 

The vast majority of COVID-19 patients in the hospital have not been fully inoculated against the disease. Many are dying. 

That’s not just anecdotal. During the spring and summer, people who were not fully vaccinated were five times more likely to be infected than someone who had completed the shots, according to a report published by the U.S. Centers for Disease Control and Prevention this month. That report also revealed that fully vaccinated people were 10 times less likely to be hospitalized, and more than 10 times less likely to die from COVID-19 than someone who had not gotten their shots. 

“The terminology, that this is a pandemic of the unvaccinated, in many ways it is true,” says Mansoor Amiji, university distinguished professor of pharmaceutical sciences and chemical engineering at Northeastern. “The majority of the cases where they develop severe disease across the United States are in those who have been unvaccinated.”

So why is it that a fully vaccinated person can get COVID-19, but is less likely to end up in the hospital? 

It’s the vaccinated immune system at work, reducing the chance that the infection could become severe.

There are a couple of things that dictate how severe a COVID-19 infection can get, Amiji says. First, if you’re exposed to a lot of virus, you’re more likely to end up with a severe infection because there will be more viral particles attacking your body. Once the virus is in your body, it will work to make more of itself. How fast it replicates will also affect how severe an infection can get. 

The vaccine protections come into play as the virus enters your system. If you’ve been vaccinated, your body has already formed antibodies that are primed to attack the spike protein on the virus, says Brandon Dionne, associate clinical professor of pharmacy and health systems sciences at Northeastern. Those antibodies will be mobilized by your immune system to bind to the invading virus in such a way that blocks it from infecting your cells. Essentially, they are soldiers tasked with neutralizing a threat.

If you have been exposed to a lot of virus, you’re going to need a lot of antibodies to stamp it all out. In someone who has not been vaccinated or infected before, the immune system will have to figure out how to make those antibodies before it can begin producing them, which could waste valuable time. 

Even if your immune system does have antibodies at the ready, some of the virus may still make it past this defense and infect your cells. That begins the replication process, which threatens to flood your body with more virus. But at the same time, your immune system will be ramping up antibody production and mounting other immune defenses to block replication and attack any new virus if it does manage to make more of itself. If you’re vaccinated, your immune system already knows how to do this and can begin the process more quickly.

“You may have no symptoms whatsoever if you’re infected after being vaccinated,” Dionne says. “But even if you do, they’re likely to be more mild because your immune system is able to respond quickly to the virus.”

In other words, it’s prepared. The vaccines have trained and outfitted your immune system for such a battle. 

The speed with which your body can attack the virus isn’t just about preventing it from making more of itself, though, Dionne says. “COVID-19 has these two steps. The first is the initial viral replication phase. In some people, that’s the flu-like illness and respiratory symptoms,” he explains. “And then in some cases, it can progress to a second response, a hyper-inflammatory response.”

It’s that second phase that is typically when the symptoms get really severe and a patient might need to be intubated, which often means that they are on death’s door. The goal, Dionne says, is to prevent the infection from shifting into that hyper inflammatory response. “And that’s usually going to happen more so in people who didn’t have an adequate immune response to the virus up front.”

That also holds true when you look at which fully vaccinated patients end up hospitalized, Dionne says. Vaccinated people who end up hospitalized with COVID-19 tend to have other risk factors or be immunocompromised in some way such that they might not have had a strong and adequately fast immune response.

Variants have thrown a bit of a curveball for this process. The vaccine teaches your body to produce antibodies designed to block the original SARS-CoV-2 spike protein. As the virus mutates, those antibodies might not be such a perfect match anymore. As a result, it may take more antibodies to effectively neutralize the virus, Amiji says. But, as of now, there are no known variants that are a complete mismatch and can dodge the vaccine protections to a dangerous degree.

Breakthrough infections have also prompted concern about the extent to which vaccine protections may wane over time. Indeed, studies of the Pfizer-BioNTech vaccine suggest that protections wane slightly around eight months after someone receives their second shot. That company has also advocated for a third shot to be administered around that time. The federal Food and Drug Administration authorized booster shots of the vaccine for seniors and high-risk individuals on Wednesday.

There are still unanswered questions about what will happen in the future, but another study published this month by the CDC found that all three U.S.-authorized vaccines were collectively 86 percent effective in preventing hospitalization in patients this summer. The Moderna coronavirus vaccine clocked in as the most effective at preventing hospitalization, at 95%, followed by Pfizer-BioNTech at 80%, and Johnson & Johnson at 60%. 

“This is incredibly encouraging,” Amiji says. “It’s incredible to see that even after such a long period of time, the evidence is so strong towards vaccines.”

At the time of publication, 54.9% of the entire U.S. population had been fully vaccinated, according to the CDC.

For media inquiries, please contact Marirose Sartoretto at m.sartoretto@northeastern.edu or 617-373-5718.