Not long after the first wave of COVID-19 infections hit, doctors all around the world began to notice something strange – a host of lingering effects persisting in patients, long after they appeared to have otherwise recovered from the virus.
These unusual neurological symptoms – encompassing fatigue, memory loss, confusion, and other abnormalities – are sometimes known as 'brain fog' or 'COVID brain', and new research may have identified an underlying cause of the condition.
"We were initially approached by our colleagues in critical care medicine who had observed severe delirium in many patients who were hospitalised with COVID-19," says neuro-oncologist Jessica Wilcox from the Memorial Sloan Kettering Cancer Centre (MSK) in New York.
"That meeting turned into a tremendous collaboration between neurology, critical care, microbiology, and neuroradiology to learn what was going on and to see how we could better help our patients."
As part of the new study, Wilcox and fellow researchers screened the cerebrospinal fluid of 18 cancer patients who were experiencing neurological dysfunction (aka encephalopathy) after having been infected with the SARS-CoV-2 virus.
Initially, it was suspected that an ongoing viral infection might be the cause of their brain fog symptoms, but microbiological analysis of fluid taken in spinal taps did not reveal any sign of the virus, suggesting the patients had recovered from COVID-19.
Nonetheless, the search did turn up an important clue as to what was going on.
"We found that these patients had persistent inflammation and high levels of cytokines in their cerebrospinal fluid, which explained the symptoms they were having," explains MSK researcher and co-first author of the study, Jan Remsik.
Cytokines are a broad category of proteins that are involved with signalling in the immune system.
A similar phenomenon showing high levels of inflammatory cytokines is sometimes seen as a side effect of chimeric antibody receptor (CAR) T cell therapy, an immunotherapy treatment, which can also produce confusion, delirium, and other neurological effects that bear a resemblance to COVID brain fog.
The thinking is that the flood of these inflammatory chemicals in the immune system seeps into the brain, producing symptoms of encephalopathy as seen in patients.
While this is the largest study to date to demonstrate this potential link between COVID-19 and post-infection neurological effects, we'll need a lot more data to untangle this association.
That said, the findings here suggest anti-inflammatory drugs might be helpful in mitigating brain fog in patients, and could highlight new directions in terms of diagnosing this strange, lingering malaise.
"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," MSK neuro-oncologist Adrienne Boire explains.
"But the more we look, the more we find connections between the two."
The findings are reported in Cancer Cell.