“Brain fog” has emerged as one of the most commonly reported symptoms that continues to linger long after recovering from COVID-19. Characterized as a “hazy” feeling of mild confusion, headaches, and short-term memory loss, the cause of this lurking side-effect defied a solid explanation for some time, but a new study in cancer patients argues it has found a likely culprit: inflammatory particles in the liquid surrounding the brain and spinal cord, the cerebrospinal fluid.

As per the new research, reported in the journal Cancer Cell, researchers from Memorial Sloan Kettering Cancer Center (MSK) in New York City details 18 cancer patients who were hospitalized with COVID-19 and experienced severe neurologic problems. All the patients were given a range of brain scans, such as MRIs, CTs, and electroencephalogram (EEG) monitoring, while 13 of the patients received a spinal tap to obtain a sample of cerebrospinal fluid.  

They found that the patients continued to have high levels of cytokines, signaling molecules secreted from immune cells that are involved in inflammation, in their cerebrospinal fluid weeks after their initial infection. 

"We found that these patients had persistent inflammation and high levels of cytokines in their cerebrospinal fluid, which explained the symptoms they were having," Dr Jan Remsik, the paper's co-first author, said in a statement. 

The researchers note that the patterns of inflammation in cancer patients with COVID-19 are comparable to those seen in non-infected people who have received CAR T cell therapy, a cancer therapy that causes immune cells to pump out cytokines. People with CAR T cell therapy also tend to experience delayed neurological effects, just like some people with COVID-19.

The virus itself, however, was not found in the cerebrospinal fluid and the brain scans did not show anything of much significance. Some theories about brain fog had suggested that the neurological symptoms of COVID-19 were caused by SARS-CoV-2 attacking the brain directly. While there is some evidence the virus can infiltrate the brain in some severely ill patients, this new research suggests that this isn’t necessarily the cause of brain fog in most people. 

However, the presence of cytokines in the cerebrospinal fluid does indicate that immune cells are able to cross the blood-brain barrier and enter the central nervous system, which the researchers say could provide some insights into how cancer cells spread to the brain.

"We used to think that the nervous system was an immune-privileged organ, meaning that it didn't have any kind of relationship at all with the immune system. But the more we look, the more we find connections between the two," added Adrienne Boire, study author, and physician-scientist at MSK.

It’s worth considering that cancer patients, in particular, are at heightened risk of severe infections from COVID-19 because of their immunocompromised state and the findings might not necessarily translate to the wider population. Nevertheless, the researchers argue that their findings do shed some light on the wider issue of brain fog and suggest that anti-inflammatory drugs and treatment, such as steroids, may help within the “management of neurologic complications of COVID-19 infection.”