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What does long-COVID predict? Study led by Seattle researchers provides some answers


ISB President James Heath. (ISB photo)

What causes some people with COVID-19 to develop the often debilitating symptoms of long COVID, with its various consequences such as brain fog, weakness and fatigue? A new study led by researchers at Seattle’s Institute of Systems Biology provides some answers, identifying factors that may predict which patients will continue to suffer from longer-term illness.

The researchers closely followed a group of 209 COVID-19 patients, seen at the Swedish Medical Center or affiliated clinics. Their symptoms were detected up to two to three months after diagnosis and their blood was analyzed for everything from immune cell composition to types of antibodies.

The researchers also performed some of their analyzes on a separate group of 100 COVID-19 patients. The study is an “in-depth assessment,” he said. Eric Topol, Professor of Molecular Medicine at Scripps Research, in a tweet. The data were compared with results from healthy people.

The researchers report that four factors present at the initial diagnosis expected the development of long-COVID. Pre-existing type 2 diabetes predicted the condition, as well as the presence of certain “autoantibodies” that attack the body, which are common in autoimmune diseases such as lupus. Some of those auto-antibodies can affect the immune system and interfere with the ability to fight COVID-19, said lead author and ISB president James Heath in an interview with GeekWire.

A third factor was the presence of COVID-19 RNA in the blood, instead of just the saliva, which was present in 25% of patients.

A fourth factor involved another virus, Epstein Barr virus, which occurs in about 90% of people but generally lies dormant in cells. Fourteen percent of patients had evidence of active Epstein Barr virus in their blood, as detected by DNA, and those patients were more likely to develop long-term COVID-19. “It seems that the COVID infection in some patients can trigger that virus,” Heath said.

Epstein Barr virus, which is the cause of mononucleosis, “mono”, is associated with fatigue. Lung COVID has a patchy onset of symptoms, from gastrointestinal problems to odor loss, but fatigue is the most common, Heath said. The link with Epstein Barr virus corresponds to another study indicating that it “wakes up” in people who continue to develop long-lasting COVID.

In general, people with long-term COVID showed “generally” signs of highly active immune system activity, Heath said, consistent with other studies. The researchers were also able to place people with long-covid in different farms categories based on their mixture of immune cells and other measurements.

The new study proposes ways for future research on ways to prevent or combat long-COVID.

Antiviral drugs may help ward off long-term COVID, given the signs of COVID-19 or Epstein Barr virus in patients’ blood, the researchers noted. Some patients with long COVID have had low levels of the hormone cortisol, suggesting that cortisol replacement therapy may be investigated.

“Lupus treatments can probably have high relevance,” Heath added. “This is an excellent area for further exploration.” Biotechnology Company Resolve Therapeutics is testing that question with an experimental remedy against Lupus in a clinical trial for prolonged COVID, administered by Fred Hutchinson Cancer Research Center.

James Heath and his colleagues discuss their new findings on long-COVID.

Estimates differ on the occurrence of prolonged COVID. One recent analysis of 57 studies found that more than half of the COVID-19 survivors had, on average, at least one symptom at 2 to 5 months. However, prevalence analysis involved mainly hospitalized, unvaccinated individuals earlier in the pandemic.

Eventually, most people’s symptoms disappear, Heath said. But he estimates that about 10% have long-term problems that last from six months to a year, and others struggle longer.

Studies evaluating the efficacy of vaccines in the prevention of long-COVID have only recently emerged. One recent study analyzes COVID-19 in healthcare professionals who have received two doses of the Pfizer / BioNTech vaccine; 19% of those with a “breakthrough” infection showed persistent symptoms at six weeks.

Larger studies are needed to back up the new study and explore treatment options.

The study was published in the journal on Tuesday Cell and involved researchers at other institutions, including Swedish Medical Center, Fred Hutchinson Cancer Research Center, and the University of Washington. Researchers at Seattle Biotechnology Company Adaptive Biotechnologies also contributed.

Other recent studies by Seattle researchers examined questions such as the response to vaccines and how the virus evades immunity. Some of these studies are listed below.

  • Researchers in the laboratory of David Veesler at the University of Washington has been particularly busy lately. In Science, he and his colleagues watched as the Delta and Kappa variants apparently evolved to evade recognition by antibodies.
  • Veesler and colleagues also looked closely at how an antibody that is the base sotrovimab, a COVID-19 treatment, binds to its target in the body. The findings, published this week in Science, helps explain why other antibody treatments work poorly against Omicron.
  • The Veesler laboratory also led a project to identify a human antibody it has the potential to developed into a therapy that can stop a wide range of COVID-19-causing and other coronaviruses.
  • The UW researchers also explore recently the antibody response in people with breakthrough infections with the Omicron and other variants. They had reactions after vaccination, infection or a mixture of the two examined in a study in Cell.
  • By Fred Hutch, researchers led by Leu Ping Zhao mutations identified in COVID-19 viruses from early in the pandemic that apparently increased the chance of serious illness.
  • James Heath and his colleagues too recently viewed that COVID-19 infection increases the risk of premature birth, low birth weight and stillbirth in pregnant women.





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