Research Roundup: COVID-19 Brain Fog and More

Brain Fog

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.

What’s Behind “Brain Fog” in COVID-19 Patients

One of several unusual symptoms reported in COVID-19 patients is what is being informally dubbed “brain fog” or “COVID brain,” but in medical terminology is called encephalopathy. It appears to be loss of short-term memory, headaches and confusion. At its most severe, it is associated with psychosis and seizures. Typically, if seen at all, it occurs weeks after first showing symptoms of COVID-19. Researchers at Memorial Sloan Kettering Cancer Center published research in the journal Cancer Cell that they believe explains the underlying cause of the brain fog.

The research team notes that this is a side effect in patients who receive CAR-T immunotherapy for certain types of cancer, which is caused by the release of cytokines by immune cells. They didn’t know for certain if that was the case with COVID-19, but since a cytokine storm is a well-observed symptom in many COVID-19 cases, it was certainly possible. They conducted a full neurological workup, including MRS and CTs and EEG on 18 patients hospitalized with COVID-19 and who were experiencing severe neurologic problems. Those all turned up negative, so they devised a test to evaluate SARS-CoV-2, the virus that causes COVID-19, in cerebrospinal fluid. Thirteen out of the 18 patients had spinal taps, but again, no virus was identified in the fluid. The fluid was then analyzed by MSK physician-scientist Adrienne Boire in the Human Oncology and Pathogenesis Program.

Jan Remsik, a research fellow in Boire’s lab, says, “We found that these patients had persistent inflammation and high levels of cytokines in their cerebrospinal fluid, which explained the symptoms they were having.”

The inflammatory markers in the COVID-19 patients were similar, but not identical, to what has been observed in cancer patients receiving CAR-T therapy, and as with CAR-T therapy, the neurologic effects are sometimes delayed.

How SGLT2 Inhibitors Work to Treat Type 2 Diabetes

A relatively new type of type 2 diabetes drug known as SGLT-2 inhibitors, are very effective, but until recently, their mode of action was not completely understood. Researchers at the Medical University of Vienna used MRI to show a direct correlation between the elimination of glucose by way of the kidneys and new glucose production in the liver. The SGLT-2 inhibitor appears to exactly balance out an increase in new glucose production in the liver. Working with AstraZeneca’s Farxiga (dapagliflozin), they found that short-term, the additional glucose produced in the liver exactly matched the amount lost in the urine due to the action of the drug. They believe that the increased glucose elimination by way of the kidneys immediately triggered regulatory mechanisms that affect the metabolism in several organs.

Using Nanoparticles to “STING” Tumors

Researchers with the University of Texas Southwestern Medical Center developed a new nanoparticle-based drug that can stimulate the body’s innate immune system and help it be more effective at fighting tumors. It targets the immune molecule STING with nanoparticles that are approximately one millionth of the size of a soccer ball. STING stands for “stimulator of interferon genes,” and the protein was discovered in 2008. It helps mediate the body’s innate immune system. The team designed a polymer that effectively delivered cyclic GMP-AMP, a natural small molecule activator of STING, to the protein target. One of the polymers they created, PC7A, had an unexpected effect—it activated STING without cGAMP. They now know that PC7A binds to a different site on the STING molecule than other known drugs, and its effect on the STING protein is different. It appears to form polyvalent condensates with STING for more than 48 hours, compared to existing drugs that activate STING over about six hours. This longer time creates a more sustained effect on STING, which leads to a more effective T-cell response against cancer cells.

Goldenseal May Compromise Glucose Control in Diabetics on Metformin

Metformin is one of the most common treatments for prediabetes and type 2 diabetes—it is the most-prescribed oral glucose-lowering drug in the world. Goldenseal is an herb used as a dietary supplement for things like cold, respiratory tract infections, hay fever, ulcers and upset stomach. A study out of Washington State University found that after taking about six days of goldenseal decreased the amount of metformin in the body by 25%--meaning that diabetics taking both might be sabotaging their attempts to control their blood glucose levels. Goldenseal is often combined with Echinacea in herbal remedies for the common cold.

Higher Nighttime Blood Pressure Seems to Increase Alzheimer’s Risk

Researchers at Uppsala University found that people whose blood pressure increased at night had a higher risk of Alzheimer’s disease. It’s more common for blood pressure to drop at night, called “dipping.” But in some people the pattern is reversed, called “reverse dipping.”

“The night is a critical period for brain health,” said Christian Benedict, associate professor at Uppsala University’s Department of Neuroscience, and senior author of the study. “For example, in animals, it has previously been shown that the brain clears out waste products during sleep, and that this clearance is compromised by abnormal blood pressure patterns. Since the night also represents a critical time window for human brain health, we examined whether too high blood pressure at night, as seen in reverse dipping, is associated with a higher dementia risk in older men.”

They found that the risk of a dementia diagnosis was 1.64 times higher among men with reverse dipping compared to normal dipping. It primarily increased the risk of Alzheimer’s, the most common type of dementia. The research cohort only consisted of older men, so they need to duplicate it in older women. They also want to investigate if taking blood-pressure-lowering drugs at night can decrease older men’s risk of developing Alzheimer’s disease. The research was published in the journal Hypertension.

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