It’s one of the many mysteries about the long Covid: who is most likely to develop it? Are some people more likely than others to experience physical, neurological or cognitive symptoms that can surface, or persist for months after their coronavirus infections are over?
Now, a team of researchers who followed more than 200 patients for periods of two to three months after they were diagnosed has reported identifying biological factors that can help predict whether a person will develop long-term Covid.
The study, published Tuesday in the scientific journal Cell, found four factors that could be identified early in a patient’s coronavirus infection and appear to correlate with an increased risk of having lasting symptoms later on.
The researchers said they found an association between these factors and long-term Covid (which is medically called Post-Acute Sequelae of Covid-19, or PASC), whether the initial infection is mild or severe. They said the findings could point to ways to prevent or treat some cases of long-term Covid, including the possibility of giving patients antiviral drugs soon after an infection is diagnosed.
“It’s the first really solid attempt to develop some biological mechanisms for long-term Covid,” said Dr Steve Deeks, a professor of medicine at the University of California at San Francisco who was not involved in the study.
He and other experts, as well as the study’s authors, cautioned that the findings are only preliminary and would need to be verified through considerably more research.
Still, Deeks said, “they’ve identified these big four factors. Each is biologically plausible, compatible with theories that other people are developing, and importantly, all four can be countered. If these pathways are confirmed, we as clinicians will be able to create interventions that make people better. That’s the important message of the research.”
One of the four factors the researchers identified is the level of coronavirus RNA in the blood in the early stages of an infection, an indicator of viral load. Another is the presence of certain autoantibodies, antibodies that attack body tissues unduly, the way they do with diseases like lupus and rheumatic arthritis. A third factor is the reactivation of the Epstein-Barr virus, a virus that infects most people, usually when they are young, and then lies dormant.
The final factor is having type 2 diabetes, although researchers and other experts say that studies involving large numbers of patients may suggest that diabetes is just one of several medical conditions that increase the risk of long-term Covid.
“I think this research emphasizes the importance of conducting measurements early in the course of the disease 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, research director for the study and president of the Institute. for Systems Biology, a Seattle-based nonprofit biomedical research organization.
“Once it becomes possible to measure something, you start being able to do something about it,” Heath said, adding that “we did this analysis because we know patients go to the doctor and say they’re feeling tired all the time, or something like that.” , and the doctor just tells them to get more sleep. That doesn’t help much. So we wanted to have a practical way to quantify and say that there is indeed something wrong with these patients.”
The complex study had several components and involved dozens of researchers at several universities and research centers, including the Institute for Systems Biology, the University of Washington, and the Swedish Medical Center in Seattle, where the study’s lead medical author, Jason Goldman , specializes in infectious diseases.
The primary patient group included 209 people aged 18 to 89 who were infected with the coronavirus in 2020 or early 2021 and who were treated at the Swedish Medical Center or an affiliated clinic. Many were hospitalized because of the initial infection, but some were treated only as medical patients. Researchers analyzed blood and nasal mucus samples when patients were diagnosed, during the acute phase of their infections, and two or three months later.
They surveyed patients for 20 symptoms associated with long-term Covid, including fatigue, labored breathing and difficulty thinking, and corroborated the reports through electronic health records, Heath said.
He said 37% of patients had reported three or more symptoms of long-term Covid in the two to three months following infection. Another 24% reported one or two symptoms, and 39% did not report any symptoms. Of patients who reported three or more symptoms, 95% had one or more of the four biological factors identified in the study when they received their Covid-19 diagnoses, Heath said.
The most influential factor appears to be autoantibodies, which are associated with two-thirds of long-term Covid cases, according to Heath. Each of the other three factors appeared in about a third of the cases, he said, and there was considerable overlap, with several factors identified, in some patients.
“The study is large and comprehensive, and a great resource for the research community studying long-term Covid,” said Akiko Iwashi, an immunologist at Yale University who was not involved in the research.
Avindra Nath, a physician and director of the department of nervous system infections at the US National Institute of Neurological Disorders and Stroke, who was not involved in the study, called it well designed but pointed to several weaknesses, including the the fact that the patients were followed for only two or three months. “It may have been too short a period,” he said. “Some of them may just spontaneously improve over time.”
Iwasaki pointed out that 71% of patients in the primary group had been hospitalized, which limits the ability to conclude that biological factors are equally relevant for people who experience mild initial infections.
One persuasive conclusion, several experts said, was the suggestion that since patients with heavy viral loads early in the process often develop long-term Covid, treating them with antivirals soon after diagnosis can help prevent long-term symptoms.
“The faster a person can clear the virus, the less likely they are to develop a persistent virus or autoimmunity, which can drive long-term Covid,” Iwasaki said.
Translation by Paulo Migliacci.
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