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Brain Fog in COVID-19 Linked to Inflammatory Markers in the Cerebrospinal Fluid

BRAIN fog is one of many neurological symptoms associated with coronavirus disease (COVID-19), but it is not understood what causes this symptom to linger after a patient’s COVID-19 is treated. Now, researchers from Memorial Sloan Kettering Cancer Center (MSKCC), New York City, New York, USA, have identified inflammatory molecules in the cerebrospinal fluid (CSF) of patients with COVID-19 that may elucidate the reason.

Characterised by confusion, headaches, and loss of short-term memory, brain fog, medically termed encephalopathy, typically emerges weeks following the initial symptoms of COVID-19. When patients first presented to MSKCC, it was believed that the virus itself was directly affecting the brain and causing symptoms such as delirium. To investigate whether this was true, a multidisciplinary team from MSKCC analysed the results from full neurology workups, including MRI, CT, and electroencephalogram monitoring, of 18 patients who were being treated at the hospital for COVID-19 and severe neurological symptoms. The full neurology workups were unremarkable, which led to the researchers taking CSF samples from the patients (n=13) and testing them for the presence of the severe acute respiratory coronavirus-2 (SARS-CoV-2) virus, the causative virus of COVID-19. The results, however, did not show that the virus was present in the fluid, so the samples were further analysed. “We found that these patients had persistent inflammation and high levels of cytokines in their CSF, which explained the symptoms they were having,” summarised first author Dr Jan Remsik.

Interestingly, the inflammatory markers observed in the patients’ CSF were similar, but not identical, to those seen in patients who had received chimeric antibody receptor (CAR) T-cell therapy, patients of whom also can experience similar delayed neurologic symptoms as a side effect to the therapy. Additionally, the cytokine storm often reported in COVID-19 is similar to the initial immune response seen in CAR T-cell therapy. Drawing on these similarities, the researchers at MSKCC treated the patients with COVID-19-associated neurological symptoms with steroids, similar to treatment for patients with neurological symptoms after CAR T-cell therapy, and reported that the patients may have benefitted from them. While it is not proven whether anti-inflammatory drugs such as steroids are safe or efficacious in this setting, this preliminary research does suggest that they may be useful and further research is warranted.