Understanding ‘brain fog’ in people with COVID-19

In the Feb. 8, 2021, issue of Cancer Cell, a multidisciplinary team from Memorial Sloan Kettering (MSK) reported an underlying cause of brain fog in COVID-19 patients: the presence of inflammatory molecules, or cytokines, in cerebrospinal fluid. COVID brain is similar to symptoms in patients receiving CAR T cell therapy for blood cancer. When CAR T cell therapy is given, it causes immune cells to release cytokines, which help the body to kill the cancer. But cytokines can seep into the area around the brain and cause inflammation. However, when the MSK team first began studying COVID brain, they didn't know that cytokines were the cause. They first suspected that the virus itself was having an effect on the brain. They studied 18 patients who were hospitalized at MSK with COVID-19 and were experiencing severe neurologic problems. The patients were given a full neurology workup, including brain scans like MRIs and CTs and electroencephalogram monitoring, to try to find the cause of their delirium. When nothing was found in the scans that would explain their condition, the researchers thought the answer might lie in the cerebrospinal fluid. Thirteen of the 18 patients had spinal taps to look for the virus, but it was not found. The rest of the fluid was taken to the lab of MSK physician-scientist Adrienne Boire for further study. “We found that these patients had persistent inflammation and high levels of cytokines in their cerebrospinal fluid, which explained the symptoms they were having,” Remsik said. The findings suggest that anti-inflammatory drugs, such as steroids, may be useful for treating the condition, but more research is needed.

AD diagnostics could become more accessible

A team of Russian researchers has summarized potential metal-containing diagnostic agents for positron emission tomography (PET), magnetic resonance imaging (MRI), and single-photon emission computed tomography (SPECT) imaging of Alzheimer’s disease (AD). Currently used radionuclides carbon-11 and fluorodeoxyglucose are difficult to synthesize and have a short lifespan. According to the researchers, metal-containing radiopharmaceuticals are not only highly effective for detecting early markers AD, but also synchrotron-independent and long-lived. Therefore, their use could improve access to diagnostic imaging of AD. The authors point out that copper, zinc and iron cations have been proven to bind to amyloids, highlighting amyloid plaques, raising the possibility of designing copper, zinc and iron-based metal complexes for the diagnosis and theranostics of AD. Among the variety of compounds considered in the review, the most promising results were shown by copper-based coordination compounds for PET imaging, gallium-based coordination compounds for MRI, and technetium-based coordination compounds for SPECT imaging. The review was published Dec. 2, 2020, in the International Journal of Molecular Sciences.

Careful with that BBB

Investigators at Weill Cornell Medical College have used detailed transcriptomic analysis to analyze induced pluripotent stem cell-derived brain microvascular endothelial cells (iBMECs), and found that cells produced according to widely used protocols lack key features of the endothelial cells that comprise the blood-brain barrier (BBB). Such cells, the authors wrote, were “deficient in vascular lineage genes while expressing clusters of genes related to the neuroectodermal epithelial lineage.” Cells could be coaxed into more closely resembling BBB cells by the forced expression of several transcription factors. Such cells “recapitulate certain vascular functions, albeit lacking expression of some organotypic transporter genes and high electrical resistance in vitro,” the authors wrote. “Nevertheless, they represent a crucial step toward the generation of an in vitro model suitable for physiological and pharmaceutical studies of the blood-brain barrier.” They published their findings in the Feb. 8, 2021, online issue of the Proceedings of the National Academy of Sciences.