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What’s causing COVID brain fog?

March 25, 2021

Woman with mask for COVID 19

COVID brain fog isn’t the general malaise we’re all feeling from a year of lockdown. It’s a catch-all term for neurological conditions seen in patients long after a COVID-19 diagnosis, including confusion, headaches, and loss of short-term memory. It’s also something of a mystery.

Scientists are considering at least two possible explanations for the condition, both centering on normal bodily substances gravitating to the brain. In one case, it’s immune cell proteins, and in the other, bone marrow cells.


The immune cell hypothesis

Even though COVID-19 is not cancer, the Memorial Sloan Kettering Cancer Center may be onto an explanation – in part because COVID fog looks like a cancer-related condition researchers there have seen before.

MSK recently studied 18 patients who had neurological problems after their positive tests for COVID-19. Standard scans like MRIs and CTs as well as brainwave monitoring (EEG)  turned up no clues to what was causing the COVID fog. A look at the cerebrospinal fluid of 13 of the patients showed no presence of the SARS-CoV-2 virus. Upon further analysis, MSK discovered that the cerebrospinal fluid of the brain fog patients has similarities to that of cancer patients who have been treated with chimeric antigen receptor (CAR) T cell therapy for blood cancer. Specifically, the fluid has an overabundance of proteins called cytokines.

In CAR T cell therapy, immune cells from a patient are removed from the body, armed with new proteins that recognize cancer, and given back to the patient in large numbers. When administered, it causes immune cells to release cytokine molecules that help the body kill the cancer. But cytokines can seep into the area around the brain and cause inflammation.

Jan Remsik, the research fellow who led the fluid analysis, “took the tools that we use in cancer biology and applied them to COVID-19,” said MSK physician-scientist Adrienne Boire.

There’s one more twist: The treatment for CAR T inflammation is steroids, which also happens to be a treatment for COVID-19. So, the researchers think it might be possible that they are already helping some COVID-19 patients neurologically. More research is needed, they say.

Blood cell hypothesis

Pathologists at Johns Hopkins Medicine in Baltimore and Brigham and Women’s Hospital in Boston have found evidence that large bone marrow cells known as megakaryocytes may be responsible for the brain fog. They suggest that megakaryocytes migrate to the brain in a journey precipitated by the destructive activity of the novel coronavirus.

“There, the researchers believe, the out-of-place cells may reduce or completely block the flow of nourishing blood through individual capillaries in the cerebral cortex,” says a Johns Hopkins Medicine news release. “Such capillary occlusions, they say, could lead to neurological impairment.”

CSF and brain tissue available for research

These studies relied on cerebrospinal fluid and brain tissue, both of which are available through the iSpecimen Marketplace. They are among a wide range of biofluids, tissue and cells available from patients who have had COVID-19 or other conditions.

iSpecimen has been deeply engaged in efforts to fight the pandemic, actively collecting biospecimen samples from patients and recovered patients for use by the CDC and others. As vaccinations mount and herd immunity looms as a possibility for the near future, we’ll continue to support researchers as they seek treatments for all of COVID-19’s symptoms.

Learn about the iSpecimen Marketplace where you can browse millions of richly annotated, de-identified human tissue and biofluid biospecimens, in addition to hematopoietic and immune cell products and COVID-19 samples. You can join for free and creating a login is easy. Request a quote or custom collection today.