(The Hill) – Long COVID-19 has had an air of mystery around it for months. Doctors have struggled to explain or understand why some people who contract COVID-19 end up having lingering symptoms like fatigue, difficulty thinking clearly, or shortness of breath weeks or even months later.  

A new study published in the journal Cell helps shed some light on the condition, for the first time identifying four factors that can help predict whether someone will develop long COVID-19.

“Being able to identify the factors that can cause the disease, cause the chronic condition, is the first step towards defining that it actually is a condition that can be treatable,” Jim Heath, president of the Institute for Systems Biology in Seattle, and an author of the study, said in an interview. “And then some of these factors also are in fact the kind of things one can imagine developing treatments for.” 

The most important factor the study identified in predicting long COVID-19 is the presence of certain kinds of antibodies called autoantibodies, which mistakenly attack healthy parts of the body. Autoantibodies are associated with autoimmune diseases, like lupus, where your immune system attacks your own body.  

But someone does not have to have an autoimmune disease to have autoantibodies present and be at higher risk for long COVID-19, Heath said.  

“Most people that have autoantibodies don’t really know it,” he said. “They’re what you call subclinical … maybe you have a risk of some autoimmune disease but it hasn’t developed.” 

Still, he said one practical application of the study is that lupus treatments could be “worth exploring” as treatments for long COVID-19.  

The second factor that can lead to long COVID-19 is the reactivation of a different virus called Epstein-Barr Virus (EBV), which is extremely common, infecting up to 90 percent of people at some point, and often causes only mild symptoms. 

The virus usually becomes inactive in the body following the initial infection, but it can be reactivated when someone gets COVID-19, helping lead to long COVID-19 symptoms.  

Heath said EBV could become reactivated when the immune system is distracted by fighting COVID-19.  

“It could be that the large distraction that’s COVID-19 infection is taking that attention away,” he said.  

The third factor identified is how much of the virus that causes COVID-19, officially called SARS-Cov-2, is present in the blood, known as the “viral load.” 

This factor along with the role of EBV suggests that new antiviral drugs that fight the immediate effects of COVID-19 infection, like the Pfizer pill Paxlovid, might also be useful in treating long COVID-19.  

“Two of these predictive factors are virus levels that are in the blood,” Heath said. “So that suggests that these antivirals that are being used to treat acute disease probably have a role for long COVID as well.” 

The final of the four factors that can predict long COVID-19 is more easily identifiable: if a patient has Type 2 diabetes.  

While these four factors are a step forward in understanding what causes long COVID-19 and helping develop treatments, the mechanism for why they are associated with long COVID-19 is still not fully clear.  

“They have a flavor of mechanistic factors,” Heath said. “The actual mechanism is not clear.” 

The study followed 309 COVID-19 patients, taking blood and swab samples at different points in time.  

In addition, one way to likely cut the risk of long COVID-19 is vaccination. A separate study from the United Kingdom found that vaccinated people were 41 percent less likely to develop long COVID-19.