New research suggests 4 factors that may increase the chances of prolonged COVID

It’s one of many mysteries about long-lasting COVID: Who is more likely to develop it? Are some people more likely than others to experience physical, neurological or cognitive symptoms than may appear or linger for months after their coronavirus infections have disappeared?

Now, a team of researchers who followed more than 200 patients for two to three months after their COVID diagnosis report that they have identified biological factors that can help predict whether a person will develop long-term COVID.

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

The researchers said they had found a link between these factors and long-term COVID (which goes by the medical name post acute sequelae of COVID-19, or PASC), whether the original infection was severe or mild. They said the results could suggest ways to prevent or treat some cases of long-term COVID, including the possibility of giving people antiviral drugs shortly after an infection has been diagnosed.

“This is the first real solid attempt to come up with some biological mechanisms for long-term COVID,” said Dr. Steven Deeks, a professor of medicine at the University of California, San Francisco, who was not involved in the study.

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He and other experts, along with the study’s authors, warned that the results were exploratory and would need to be verified by significantly more research.

Yet Deeks said, “They have identified these four main factors. Each is biologically plausible, in line with theories that other people pursue, and more importantly, each one can be acted upon. If these pathways are confirmed, we as clinicians can actually design interventions. to make people better. That’s the message to take home. “

One of the four factors that 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 during conditions such as lupus and rheumatoid arthritis. A third factor is the reactivation of the Epstein-Barr virus, a virus that infects most people, often when they are young, and then usually goes to sleep.

The last factor is having type 2 diabetes, although researchers and other experts said that in studies involving a larger number of patients, it may turn out that diabetes is just one of several medical conditions that increase the risk of long-lasting COVID.

“I think this research underscores the importance of performing measurements early in the course of the disease to find out how to treat patients, even though we do not really know how to use all that information yet,” said Jim Heath. , rector. investigator of the study and president of the Institute for Systems Biology, a nonprofit biomedical research organization in Seattle.

“When you can measure something, then maybe you can start doing something about it,” Heath said, adding, “We did this analysis because we know patients will go to doctors and they will say they are tired. “all that time or whatever, and the doctor just tells them to sleep more. It’s not very helpful. So we would actually have a way of quantifying and saying that there is 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 the 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 aged 18 to 89 who were infected with coronavirus by 2020 or early 2021 and were cared for at the Swedish Medical Center or an affiliated clinic. Many were hospitalized due to their first infections, but some were only seen as outpatients. Researchers analyzed blood and nasal swabs when patients were diagnosed, in the acute phase of their infections and two to three months later.

They examined patients about 20 symptoms associated with prolonged COVID, including fatigue, brain fog and shortness of breath, and confirmed these reports with electronic health records, Heath said.

He said 37% of patients had reported three or more symptoms of prolonged COVID two or three months after infection. A further 24% reported one or two symptoms and 39% reported no 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 were diagnosed with COVID-19, Heath said.

The most influential factor appeared to be autoantibodies, which were associated with two-thirds of cases of long-term COVID, Heath said. Each of the other three factors appeared in about a third of cases, he said, and there was significant overlap, with several factors identified in some patients.

The researchers confirmed some of their findings in a separate group of 100 patients, many with mild initial infections, from research led by Dr. Helen Chu at the University of Washington. The researchers also compared their results with data from 457 healthy people.

“The study is large and comprehensive and is a great resource for the community studying long-term COVID,” said Akiko Iwasaki, an immunologist at Yale who was not involved in the research.

Dr. Avindra Nath, who heads the section on nervous system infections at the National Institute of Neurological Disorders and Stroke and was not involved in the study, called the study well-designed, but pointed out several weaknesses, including the fact that patients had only been followed for two to three months. “This may be too short a time frame,” he said. “Some may just want to improve spontaneously over time.”

Iwasaki noted that 71% of the patients in the primary group had been hospitalized, which limited the possibility of concluding that the biological factors were equally relevant to individuals with mild initial infections.

A compelling conclusion, several experts said, was the suggestion that because patients with high viral load early often developed long-term COVID, giving people antiviral drugs soon after diagnosis can help prevent long-term symptoms.

“The faster one can eliminate the virus, the less likely it is to develop persistent viruses or autoimmunity that can drive long-term COVID,” Iwasaki said.

That some patients had reactivated Epstein-Barr virus also made sense, Nath said, because other diseases have revived that virus, and its reactivation has been linked to conditions such as chronic fatigue syndrome, which some cases of prolonged COVID resemble, and multiple sclerosis. Deeks said it might be possible to give antiviral drugs or immunotherapy to patients with reactivated Epstein-Barr virus.

There were other exciting results that experts said needed more substantiation. One was a suggestion that because people with long-term respiratory problems had low levels of the stress hormone cortisol, they could benefit from cortisol replacement therapy, which Heath said some doctors were already trying.

In another finding, which he said could be a way to document that patients’ neurological symptoms were the result of prolonged COVID, the blood of people with lingering neurological problems contained elevated levels of proteins associated with disturbed circadian rhythms and sleep / wake cycles.

One patient in the study’s primary group was John Gillotte, 40, a software engineer who contracted coronavirus in March 2020. He was on a respirator for about six days, after which he experienced delirium in the hospital when he closed his eyes.

“I saw the devil, who was about 50 feet tall, scream at me and throw limbs, which he parted from other people,” recalled Gillotte, who later got a picture of the demon tattooed on her right arm, with depictions of hell below. and the heavens above to symbolize his progress from sickness to recovery.

Gillotte, who moved from Seattle to Manhattan last year, said that for several months after his infection, he experienced muscle weakness, lack of endurance, brain fog that weakened his concentration at work, a changed sense of smell and the perception that most food tasted like ash .

He said that before COVID he had a spontaneous ability to visualize certain colors with certain foods – pink when he sprinkled pepper, blue with a type of spirit – but now he is appalled at having lost these automatic connections.

Gillotte said he did not have diabetes and did not know if he had the other three factors because the researchers said the study protocol prevented them from revealing data on participants.

Heath noted, however, that Gillotte had been re-infected with coronavirus by October 2020, perhaps reflecting a theory that emerged from their study: that patients with higher levels of autoantibodies had lower levels of protective antibodies against coronavirus, possibly making them more vulnerable. . for re-infection.

Deeks said lower protective antibody levels could also be a pathway leading to long-term symptoms. “If you do not have a good antibody response, you are not removing the virus; you have more viruses around you, and that leads to more prolonged COVID,” he said.

Still, Heath said overall research had shown that the four biological factors intersected and overlapped, suggesting that there may be relatively straightforward ways to prevent long-term COVID early on. Months later, “all these vague symptoms are so hard to track down because you’ve somehow lost that information, but if you look back when those symptoms first trigger, it actually seems manageable.”

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