Can the vaccinated develop long COVID after a breakthrough infection?

While some breakthrough cases among those who are fully vaccinated against COVID-19 are inevitable, they are unlikely to result in hospitalization or death. But one important question about breakthrough infection that remains unanswered is: Can the vaccinated develop so-called long COVID?

Long COVID refers to a set of symptoms — such as severe fatigue, brain fog, headache, muscle pain and sleep problems — that can persist for weeks or months after the active infection has ended. The syndrome is poorly understood, but studies suggest that between 10% and 30% of adults who catch the virus may experience long COVID, including those who experienced only mild illness or no symptoms at all.

But the vast majority of data collected about long COVID has been in the unvaccinated population. The risk of developing long COVID for the fully vaccinated who get infected after vaccination has not been studied.

While preliminary research suggests that it is, in fact, possible for a breakthrough case to lead to symptoms that can persist for weeks to months, there are still more questions than answers. What percent of breakthrough cases result in lingering symptoms? How many of those people recover? Are the persistent symptoms after breakthrough infection as severe as those that occur in the unvaccinated?

"I just don't think there is enough data," said Dr. Zijian Chen, medical director at the Center for Post-COVID Care at Mount Sinai Health System in New York. "It's too early to tell. The population of people getting sick post vaccination isn't that high right now, and there's no good tracking mechanism for these patients."

One recent study of Israeli health care workers published in the New England Journal of Medicine offers a glimpse of the risk of long COVID after a breakthrough infection. Among 1,497 fully vaccinated health care workers, 39 of them — about 2.6% — developed breakthrough infections. (All of the workers were believed to be infected after contact with an unvaccinated person, and the study was conducted before the delta variant became dominant.)

While most of the breakthrough cases were mild or asymptomatic, seven out of 36 workers tracked at six weeks (19%) still had persistent symptoms. These long COVID symptoms included a mix of prolonged loss of smell, persistent cough, fatigue, weakness, labored breathing or muscle pain.

But the study's authors caution against drawing too many conclusions from the research. The sample size — just seven patients — is small. And the research was designed to study antibody levels in the infected, said Dr. Gili Regev-Yochay, director of the infectious disease epidemiology unit at Sheba Medical Center. It was not designed to study the risk of long COVID after a breakthrough infection.

"It was not the scope of this paper," Regev-Yochay said. "I don't think we have an answer to that."

Even so, the fact that 1 in 5 of the health care workers who had breakthrough infections still had lingering symptoms after six weeks appears to be the first indication from a peer-reviewed study that long COVID is possible after a breakthrough infection.

"People have said to me, 'You're fully vaccinated. Why are you being so careful?'" said Dr. Robert M. Wachter, professor and chair of the department of medicine at the University of California, San Francisco. "I'm still in the camp of I don't want to get COVID. I don't want to get a breakthrough infection."

Wachter said that despite the many limitations of the Israeli study, the data offered more evidence that the vaccinated should keep taking reasonable precautions to avoid the virus.

"I'm going to take it at face value that 1 in 5 people, six weeks after a breakthrough case, continued to feel crummy," Wachter said. "That's enough to make me want to wear two masks when I go into the grocery store, which is not that burdensome anyway."

Complicating the study of breakthrough infections is the fact that the U.S. Centers for Disease Control and Prevention only tracks post-vaccination infections that result in hospitalization or death. While the CDC does continue to study breakthrough infections in several large cohorts, the lack of data on all breakthrough cases remains a source of frustration among scientists and patient advocacy groups.

"It's very frustrating not to have data at this point in the pandemic to know what happens to breakthrough cases," said Akiko Iwasaki, an immunologist at Yale School of Medicine who is conducting studies of long COVID. "If mild breakthrough infection is turning into long COVID, we don't have a grasp of that number."

But some experts predict the surge of new cases caused by the spread of the delta variant will, unfortunately, lead to more breakthrough cases in the coming months. Chen said it will take several months before patients with long COVID from a breakthrough infection are enrolled in studies.

"We're waiting for these patients to show up at our doors," Chen said.

Despite the lack of data, one thing is clear: Getting vaccinated will reduce the risk of getting infected and getting long COVID, said Athena Akrami, a neuroscientist at University College London who collected and published data from nearly 4,000 long COVID patients after developing long COVID herself after a March 2020 bout with COVID-19.

"It's simple math," Akrami said. "If you reduce infections, then the likelihood of long COVID will drop automatically."

This article originally appeared in The New York Times.