LA CROSSE, Wis. (SPECTRUM NEWS) — Last week, reports out of La Crosse County brought up a concerning question: Can you get infected with COVID-19 more than once?

On Tuesday, the county health department included the following statement in its regular update on Facebook: “Today is the first time that an individual person has been counted in our case count twice due to reinfection, and their COVID-19 infections were more than three months apart.” In the comments section, officials added that the patient’s symptoms were different the second time around.

Since the original report, the health department has updated its language to say they are considering the case a “possible reinfection.” 

“We will continue to be as transparent as we can when reporting possible reinfections and other data,” the department posted in a follow-up statement. “This case is being evaluated by healthcare partners at this time.”

Though they remain pretty scarce, reports like this one have set off alarm bells about whether immunity to COVID-19 can last, and what that means for our “new normal.” The current Centers for Disease Control and Prevention guidelines state that “if a positive test occurs more than three months after a person’s symptom onset, clinicians and public health authorities should consider the possibility of reinfection.” But, like with many of the questions swirling about this new virus, scientists say it’s still too soon to have a clear answer about reinfection. 

“At this point, there's more we don't know than what we know,” says Jeff Pothof, chief quality officer at UW Health.

In the La Crosse case, as with many other anecdotal reports, it’s hard to tell whether this was a true reinfection or a relapse of the same infection, Pothof says. 

Other viruses have the ability to hide away in the body and then resurface later on to cause a new bout of illness, he says. For example, the virus that causes chickenpox can hunker down in the body’s tissues for years before later re-emerging to cause shingles in adults.

“We're trying to figure out, is that something that's happening with COVID-19?” Pothof says. “Or are these true reinfections, where the body was completely clear of the virus, and then they got exposed the second time, and for whatever reason, their immune system was unable to keep it under control?”

Among the respiratory viruses that are similar to SARS-CoV-2, though, this staying power isn’t common, says Mary Beth Graham, medical director of infection prevention and control for Froedtert Hospital. Respiratory viruses like influenza don’t usually act as latent viruses that can linger in the body forever, she says.

Graham says though the idea of reinfection sounds alarming, it’s actually fairly common.

“It's not unique to coronavirus,” she says. “This is not an unexpected thing to see with a viral illness.”

One thing to remember is that the immune system has multiple layers of defense, Graham says. There’s innate immunity, a generalized arm that doesn’t deal with viruses much. The main focus when we talk about viruses is the learned or adaptive arm of the immune system, which, like the name suggests, adapts to fend off specific invaders — like hostile viruses. 

The adaptive immune system produces the antibodies we’ve heard so much about in relation to COVID-19, as well as T-cells that are harder to measure but also work to neutralize specific viruses. When the body is exposed to a new virus, it can take some time to build up a response from the innate immune system, Graham explains: Usually, young people will be making antibodies within a week or so, while in older adults, the process could take a few weeks. 

Once the body has dealt with a virus once, though, the adaptive immune system is able to react more quickly if it’s exposed again. Antibodies tend to wane after some time — some studies have already shown that coronavirus patients’ antibody levels can dip within a few months of recovery — so Graham says the lingering levels might not be enough to completely stop another infection. But they should still keep people from getting as sick as they were the first time around, she says.

“It is absolutely feasible that people can get reinfected, although I would expect that it would be a more benign or less severe course of disease,” Graham says. 

The La Crosse County Health Department hasn’t yet shared the details of this patient’s symptoms and whether they were more or less severe after the possible reinfection.

Slight mutations in a virus can also allow it to slip through the immune system’s defense mechanisms a second time, Pothof says.

To identify a viral invader, the immune system looks at specific proteins on the surface of the virus, he explains. But some viruses are able to change their proteins a little bit, making it hard for the immune system to respond in time — like the common cold, which can come back in slightly different forms and infect people many times.

“For those viruses that can change or shift those proteins that our body recognizes, they tend to be better at infecting us multiple times,” Pothof says. “Our immune systems are constantly trying to relearn what that pattern is on the surface of that virus.”

The SARS-CoV-2 virus doesn’t appear to be mutating especially fast, Pothof says. The “spike protein” on its surface has appeared to stay pretty consistent so far. But again, he emphasizes that the virus is still new, and we can’t rule out the possibility that this protein could mutate.

As for the changing symptoms, Pothof says even in the case of a possible relapse, it’s “not so surprising” that patients could see different effects show up. COVID-19 presents in a huge variety of ways, he points out, and though it’s unclear exactly why, different symptoms shouldn’t yet be taken as evidence one way or the other.

There’s also the question of testing. After a person has been infected with COVID-19, the virus’s genetic material can stick around in the body for a while, even if the symptoms fade, Graham says. The PCR tests used in most labs could pick some of this viral RNA stuck in the upper respiratory tract.

“We've had patients here whose nose swab has been positive for the virus for months, even though their symptoms are totally gone,” Graham says. “It’s potentially leftover viral genome, or just remnants of dead virus that you're picking up because that PCR test is so sensitive.”

Previously, the CDC’s guidelines stated that to be considered a case of reinfection, a patient should test negative in the interim period between their two bouts of illness. But Graham says those instructions have since shifted to recognize that a positive PCR test doesn’t always indicate live virus. 

To tell whether a virus is still alive and active in the body, scientists can try to culture the virus from a patient’s sample and see if it will reproduce, Graham says. In May, researchers in South Korea did just that, looking into 285 cases where patients tested positive weeks after recovering from COVID-19. The scientists weren’t able to grow new virus from patients’ samples, and also found no evidence that these repeat infections spread to patients’ personal contacts — both good signs that the virus was no longer infectious.

Also in May, a study in macaques found that monkeys who were infected with SARS-CoV-2 once were protected from reinfection when they were exposed to the virus again. 

Results like these are promising, and reports of reinfections remain few and far between, especially considering the huge number of infections we’ve seen around the world. Still, Pothof cautions that people shouldn’t assume that “once you get it, you’re good.” 

“Thankfully, there's not a lot of these cases. But there's enough kind of suspicious cases like this where we shouldn't say that the question about immunity after initial infection with COVID-19 is completely understood, written in stone, a done deal,” Pothof says. “I don't think we can assure people that if you get COVID once, then you're immune from it for the rest of your life.”

The guidance around immunity and reinfection will probably keep evolving as scientists learn more in the coming months, Pothof says. He and Graham say more research is needed to understand the immune system’s response to this virus, and to get to the bottom of cases like this one in La Crosse.

Many people see the changing guidance about COVID-19 as frustrating, Graham says. But in her view, it’s all a sign of progress in our understanding of this still-new virus.

“Science isn't static, and the attainment of knowledge isn’t static,” she says. “Everything that we learn about this virus gives us better insight into what we need to do next.”​