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Plasma from COVID-19 patients shows who are most likely to get seriously ill – Washington University School of Medicine in St. Louis

Plasma from COVID-19 patients shows who are most likely to get seriously ill – Washington University School of Medicine in St. Louis

 



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Certain proteins in plasma signals that may eventually require ventilator face bad consequences

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Researchers at the Washington University School of Medicine in St. Louis study plasma samples from COVID-19 patients to predict who will need to be put on a ventilator to breathe and who are most likely to die from the virus. We identified specific proteins that help .

“Identifying harmful proteins may help not only in the subspecies of the virus that causes COVID-19, but also when new viruses emerge in the future,” said the principal investigator. Dr. Carlos Curchaga director of Neurogenomics and Informatics Center in medical school. “We could take blood from people with COVID and check the levels of these key proteins to quickly determine the risk of serious consequences. can be determined.”

Results will be published online in the journal iScience.

Cruchaga, who is also Barbara Burton and Reuben M. Morriss III Professor of Psychiatry, studied plasma samples from 332 COVID-19 patients admitted to the Barnes-Jewish Hospital in St. compared. SARS-CoV-2, the virus that causes COVID-19. Because the samples were taken while patients were hospitalized, proteins associated with worse COVID-19 outcomes were identified long before patients were actually put on a ventilator or died from the virus. I was.

To study proteins in plasma, researchers used a technique called high-throughput proteomics to identify protein overexpression and underexpression (also called dysregulation). Scientists conducted additional tests to distinguish between proteins that were dysregulated as a result of severe disease and proteins that actually caused severe disease.

The research team identified a number of proteins that were altered in COVID-19 patients, but the presence of any of the 32 proteins that become dysregulated during COVID-infection may result in patients requiring ventilator support. I decided that it was showing that They identified another five proteins that, if found to be altered in the plasma as a result of the virus, indicate a patient’s likelihood of death.

“Many of the proteins we identified were associated with inflammation and the body’s immune response, for example, so it was not surprising that they were altered by COVID infection.” , made patients more likely to require mechanical ventilation or die.Using these proteomic approaches, we now have a methodology that can predict problems, which is very important for clinical practice. is.”

Of the 332 COVID-19 patients studied, plasma contained any of 32 dysregulated proteins, proteins indicating that ventilation may be required for respiration Patients eventually required respiratory support, usually about 1 week after admission (82 patients). And of the 332 patients, only those who had changes in five proteins that scientists linked to severe illness eventually died from the infection (63 patients).

To further validate their findings, the researchers examined similar proteomic data from 297 COVID-19 patients and 76 controls at Massachusetts General Hospital in Boston and found that the same protein was We found that a cohort of patients indicated eventual need for ventilators and possible mortality.

This study included plasma from patients hospitalized during the initial spike in COVID-19 cases, so it is unclear whether the exact same protein leads to death from ventilation or infection from late variants of the virus. It’s not clear, Cruchaga said. But the same approach using high-throughput proteomics could likely be used to validate or identify suspect proteins in other variants, he said. he added.

The study also showed that some of the proteins that were dysregulated during COVID-19 infection were linked to pathways for coronary artery disease and Alzheimer’s disease, suggesting that COVID-19 may increase the risk of these diseases. It was confirmed that there is

“This was a surprising discovery, as the project was not focused on these issues,” Kulchaga said. “Some of the proteins we identified are Alzheimer’s disease-causing proteins, and others are used as biomarkers for Alzheimer’s disease in both blood and cerebrospinal fluid. COVID infection is associated with these biomarkers. A neurologist may even diagnose a patient with Alzheimer’s disease if they go to a doctor’s office for a blood test and have recently contracted COVID-19.

“This is a great example of how high-throughput approaches can help us understand that COVID is a disease that not only affects the lungs, but also the brain and heart.”

Kulchaga added that the study provides a biological basis for understanding some of the symptoms associated with COVID-19 over time. And he said studying these proteins in plasma could identify people who are at increased risk of developing such symptoms after COVID infection.

“Despite fewer people dying from COVID-19 these days, there are concerns about its impact on memory in people with normal cognition and its impact on disease progression in people who already have cognitive impairment.” he said.

Wang L, Western D, Timsina J, Repaci C, Song WM, Norton J, Kohlfeld P, Budde J, Climer S, Butt OH, Jacobson D, Garvin M, Templeton AR, Campagna S, O’Halloran J, Presti R, Goss CW, Mudd, PA, Ances BM, Zhang B, Sung YJ, Cruchaga C. Plasma proteomics of SARS-CoV-2 infection and severity reveal impact on Alzheimer’s disease and coronary artery disease pathways. EyeScience, March 14, 2023.

This study was funded by the National Institute on Aging, the National Cancer Institute, and the National Center for Advanced Translational Sciences at the National Institutes of Health (NIH). Approval Numbers: RF1 AG074007, R01 AG044546, P01 AG003991, RF1 AG053303, RF1 AG058501, U01 AG058922, P30 AG066444, P01 AG03991, P01 AG026276, P30 CA091842, UL1 TR00234. Additional funding has been received from the Alzheimer’s Association Research Grant, the Alzheimer’s Association Zenith Fellows Award, and the Chan Zuckerberg Initiative.

About the University of Washington School of Medicine

washuu medicine is a global leader in academic medicine, including biomedical research, patient care, and 2,800-faculty educational programs. Its National Institutes of Health (NIH) research funding portfolio is the third largest of any U.S. medical school, growing 52% over the past six years, and combined with institutional investment, WashU Medicine will invest in basic and clinical research. We commit well over $1 billion annually. innovation and training. Its faculty practices are consistently among the top five in the country, with more than 1,800 faculty physicians practicing and medical staff at his 65 locations. Barnes Jew and St. Louis Children the hospital of BJCHealthcareWashU Medicine has a storied history in MD/PhD training and recently spent $100 million on scholarships and curriculum updates for medical students, offering not only physical therapy, occupational therapy and audiology, but all medical subs. We offer specialty and first-class training programs. and communication science.


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