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medium sizeMore than three years after the COVID-19 pandemic began, more than three-quarters of adults in the United States — about 260 million people — have been infected by the infectious disease. While most people recover within a few weeks, about one in 10 people have long-term COVID-19. Dozens of symptoms have been linked to the mysterious condition, including fatigue, difficulty breathing, joint or muscle pain, chest pain, irregular heartbeat, kidney pain, tinnitus, nausea, hand tremors, depression and “brain fog.”
What contributes to the persistence of the coronavirus remains hotly debated. Researchers have raised several possibilities, including persistent reservoirs of SARS-CoV-2 particles in patients, abnormal immune responses to acute infection, and vascular damage.
The viral genome lies dormant in human blood cells.
But recently published research nature Certain biomarkers detectable in the blood related to immune and endocrine system function were identified, which may help us understand what causes long-term COVID-19 and how to diagnose and possibly even treat it. “The ability to find unique biomarkers is a big deal,” said Alexandra (Sasha) Tabachnikova, Ph.D. student in immunobiology at Yale School of Medicine and a co-author of the study.
The researchers analyzed data from 268 participants, comparing patients with long-term COVID-19 symptoms for four months or more to a group of patients who had never had COVID-19 but had been vaccinated, and another group of people who had fully recovered from COVID-19. patients for comparison. They collected blood samples from all participants and analyzed the samples to measure which immune cells were the most active. They also exposed blood samples from study participants to various viral proteins, such as SARS-CoV-2 and Epstein-Barr, as well as proteins normally found in human cells, to measure immune responses. Once they discovered the differences in patients’ blood, they used machine learning to better understand which blood differences best helped them differentiate between patients with and without long-term COVID-19 infection.
Tabachnikova and her colleagues discovered surprising patterns in the blood of long-term COVID-19 patients. They detected abnormal activity of immune cells called T cells, which help fight infections, reactivation of latent viruses in the blood, such as the Epstein-Barr virus, and sharp increases in cortisol, a hormone that regulates stress. decline.
Epstein-Barr virus causes mononucleosis and is found in the blood of 95% of people worldwide. After a person is first infected with Epstein-Barr virus, the virus may stop producing viral particles, but the genome remains dormant in the person’s blood cells. In situations of stress and reduced immune cell function, such as when a person is infected with COVID-19, the virus may reactivate and begin to multiply.
This finding is consistent with research showing that people with detectable levels of Epstein-Barr virus at the time of their COVID-19 diagnosis were more likely to experience long-term COVID-19 symptoms, such as fatigue, Mucus cough and memory problems.
The researchers also found that patients with long-term COVID-19 infection had higher levels of IL-8 and galectin-1, a protein involved in regulating inflammation, while their cortisol levels were much lower. Drops in cortisol levels are also associated with chronic fatigue syndrome, Tabachenkova said, which could explain why some of the symptoms long-term COVID-19 patients experience are similar to those of chronic fatigue syndrome.
Based on the biomarkers they identified, the researchers designed a machine learning algorithm that was able to distinguish between those with and without long-term COVID-19 in the study population with 96% accuracy. While the study population was smaller, the study paints a clearer picture of a mysterious condition. Understanding the biological mechanisms involved is one step closer to developing effective treatments. 
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