Long COVID Risk Makes It Worth Avoiding Second Infections

Dec. 19, 2022 — Alexander Truong, MD, has been seeing long COVID patients for more than 2 years but thought the numbers would have significantly dwindled by now. Instead, a steady flow of patients still shows up at the Emory Executive Park post-COVID clinic he and a colleague launched in fall 2020 in Atlanta. And among patients infected more than once, the symptoms appear worse.

“We are definitely seeing a lot of patients who, when they get reinfected, have worsening post-COVID issues. That’s very true and I think that’s a big signal,” says Truong, a pulmonologist and an assistant professor at Emory University’s School of Medicine.

COVID-19 is definitely not over, says Angela Cheung, MD, PhD, a senior physician scientist with the University Health Network and a professor of medicine at the University of Toronto. And each time someone gets infected, they risk developing long COVID. A prior infection does not erase the risk, Cheung says.

“It’s not like, ‘Oh, I’ve had one, so it’s OK. Now I can take off my mask, do what I like.’ It has health consequences for reinfections – higher mortality rate, higher hospitalization rates, higher risk of long term, lingering symptoms,” she says.

New research suggests that those infected more than once have an increased risk of developing long COVID and other health problems compared to those infected just once. But parsing out the extent of these risks – particularly with newer variants – is more complicated, Truong and other experts say, particularly when factoring in vaccinations and antiviral treatments. 

“It makes sense that repeat infections would not be beneficial to a person’s health. But I think it’s really hard to know what the additional risk of each subsequent infection would be because there are all sorts of other things in the mix,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California San Francisco.

“There are vaccines — new vaccines, old vaccines. There are variants — old variants, new variants, and now multiple variants circulating at the same time.”

Veterans Affairs Study

A large study involving the records of 5.8 million Department of Veterans Affairs patients that was published in Nature Medicine in November found that patients infected more than once had significantly higher risks of death, hospitalization, heart problems, blood clotting, long COVID, and a host of other health issues and organ damage. Notably, the study found that these elevated risks remained even 6 months after reinfection.

While the study highlights the increased risks associated with reinfections, it has its limitations. The study did not directly compare a first infection to reinfection within the same pool of patients. It only compared one group of individuals who had a single infection to a separate group who had more than one infection. 

There could be other factors that made one group more susceptible to reinfection and at greater risk of adverse health outcomes. The study also did not compare reinfection risks between different variants or subvariants.

Another limitation is the VA population itself. The VA database is extremely useful for large studies like this one because it follows a large number of people with comprehensive medical records, experts say, but the VA’s population of mostly older white males does not reflect the demographics of the general population.

Nonetheless, the message for the public is straightforward, says Cheung. “I wouldn’t get into the weeds. The big message and big picture is that reinfections are bad.”

Different Risks With New Variants?

Experts say understanding reinfection risks, particularly with the newer variants and subvariants, is complicated because more people are now vaccinated compared to earlier in the pandemic.

“There are not any definitive answers. … It’s very, very difficult to disentangle the emergence of new variants from the uptake of vaccines,” says Peluso.

“It does seem like overall there may be less long COVID with the newer variants, but it’s very hard to say whether that is a characteristic of the virus or a characteristic of the fact that most people who are getting the virus have either been vaccinated or previously infected to have some different immune baseline from somebody who’s seeing the viral antigen for the first time.”

However, consensus is growing that those who are vaccinated and end up with breakthrough infections are at lower risk of developing long COVID. One U.K. study published in the journal Open Forum Infectious Diseases in September, for example, found that people who had two COVID-19 vaccinations at least 2 weeks prior to infection had a 41% decrease in the odds of developing long COVID symptoms, compared to people who were not vaccinated at the time of infection.

“We also know that in patients who’ve had their vaccinations, they are less likely to have a reinfection, or when they do have reinfection, they’re less likely to have severe infection,” says Truong.

“That’s the one big signal that we have and that’s why I’m trying to wave the flag as much as I can about getting vaccinated [and boosted].”

While some data suggests the risks of long COVID are lower with Omicron variants compared with the Delta variant, experts point out that a far greater number of people have been infected with Omicron, so even a small percentage of a large number is still a large number. 

One study looking at Omicron versus Delta shows about half the risk, but half the risk in a lot more people is still a lot of high absolute numbers,” Cheung says, referring to a June paper published in The Lancet

She still sees a lot of patients with long COVID – some infected as recently as this past summer, some vaccinated and infected for the first time, and others coming in following reinfections.

And while Omicron variant and subvariant infections may appear milder for many people, doctors note new patients are also showing up with the same debilitating symptoms as those who got long COVID earlier in the pandemic: fatigue, shortness of breath, racing heart, brain fog, sleep disturbances, and mental health issues.

“On my post-COVID clinic days, I’m still seeing four to eight new patients who had infections in 2022 come in with significant symptoms,” says Truong.

And long COVID can kill. More than 3,500 death certificates filed from the start of the pandemic through June 2022 list long COVID as a specific cause of death, the National Center for Health Statistics reports.

Minimizing Post-COVID Risks

Peluso says what can be learned from the VA study is that repeated attacks on the immune system are dangerous and that continuing to avoid infection remains extremely important.

“The best way for someone to protect themselves against that is to avoid getting COVID in the first place,” says Peluso. It is a sentiment echoed by Truong and Cheung.

But given the transmissibility of the newest variants and subvariants and the removal of public health measures, it’s often difficult to prevent infection. Tried and true tools do, however, work: being up to date on vaccinations, wearing high-quality, well-fitted masks, advocating for good ventilation, and conducting self-testing with rapid antigen tests, particularly ahead of indoor events during busy holiday periods.

“It’s possible that this may become less common over time. I hope that’s true,” Peluso says. 

“It’s also possible that it might go the other way. And so for that reason, I’m trying to avoid all of the variants.”