If further study confirms the findings, they could lead to ways to prevent and treat the complex condition.

By Pam Belluck

It is one of many mysteries about long Covid: Who is more prone to developing it? Are some people more likely than others to experience physical, neurological or cognitive symptoms than can emerge, or linger for, months after their coronavirus infections have cleared?

Now, a team of researchers who followed more than 200 patients for two to three months after their Covid diagnoses report that they have identified biological factors that might help predict if a person will develop long Covid.

The study, published Tuesday by the journal Cell, found four factors that could be identified early in a person’s coronavirus infection that appeared to correlate with increased risk of having lasting symptoms weeks later.

The researchers said they had found that there was an association between these factors and long Covid (which goes by the medical name post-acute sequelae of Covid-19, or PASC) whether the initial infection was serious or mild. They said that the findings might suggest ways to prevent or treat some cases of long Covid, including the possibility of giving people antiviral medications soon after an infection has been diagnosed.

“It’s the first real solid attempt to come up with some biologic mechanisms for long Covid,” said Dr. Steven Deeks, a professor of medicine at the University of California, San Francisco, who was not involved in the study.

He and other experts, along with the study authors themselves, cautioned that the findings were exploratory and would need to be verified by considerably more research.

Still, Dr. Deeks said: “They’ve identified these four major factors. Each is biologically plausible, consistent with theories that other people are pursuing, and importantly, each is actionable. If these pathways get confirmed, we as clinicians can actually design interventions to make people better. That is the take-home message.”

One of the four factors researchers identified is the level of coronavirus RNA in the blood early in the infection, an indicator of viral load. Another is the presence of certain autoantibodies — antibodies that mistakenly attack tissues in the body as they do in conditions like lupus and rheumatoid arthritis. A third factor is the reactivation of Epstein-Barr virus, a virus that infects most people, often when they are young, and then usually becomes dormant.

The final factor is having Type 2 diabetes, although the researchers and other experts said that in studies involving larger numbers of patients, it might turn out that diabetes is only one of several medical conditions that increase the risk of long Covid.

“I think this research stresses the importance of doing measurements early in the disease course to figure out how to treat patients, even if we don’t really know how we’re going to use all that information yet,” said Jim Heath, the principal investigator of the study and president of the Institute for Systems Biology, a nonprofit biomedical research organization in Seattle.

“Once you can measure something, then you may be able to start doing something about it,” Dr. Heath said, adding: “We did this analysis because we know patients will go to physicians and they’ll say that they’re tired all the time or whatever, and the physician just tells them to get more sleep. That’s not very helpful. So, we wanted to actually have a way to quantify and say that there’s actually something wrong with these patients.”

The complex study had several components and involved dozens of researchers at several universities and centers, including the Institute for Systems Biology, the University of Washington and Swedish Medical Center in Seattle, where the study’s lead medical author, Dr. Jason Goldman, is an infectious disease specialist.

The primary group of patients included 209 people, ages 18 to 89, who were infected with the coronavirus during 2020 or early 2021 and were seen at Swedish Medical Center or an affiliated clinic. Many were hospitalized for their initial infections, but some were seen only as outpatients. Researchers analyzed blood and nasal swabs when patients were diagnosed, during the acute phase of their infections and two to three months later.

They surveyed the patients about 20 symptoms associated with long Covid, including fatigue, brain fog and shortness of breath, and corroborated those reports with electronic health records, Dr. Heath said.

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