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Stanford researchers link COVID brain fog to 'chemo brain'

Scientists discover long COVID may cause cognitive issues due to nerve damage in the brain
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A scan of a control sample of white matter taken for the Stanford COVID-19 brain fog experiment.

Patients experiencing COVID-19 brain fog suffer from the same sort of excessive inflammation and damage to nerves in the brain as patients with "chemo brain," a new study by Stanford University and Yale University scientists has found.

The study, which was published on June 12 in the journal Cell, found the same brain cells and processes were affected by the damage. The senior authors include Dr. Michelle Monje, professor of neurology and neurological sciences at Stanford University and Akiko Iwasaki, professor of immunology and of molecular, cellular and developmental biology at Yale University.

The experiment, which involved analysis of live mice and postmortem human brain tissue, revealed that those infected with SARS-CoV-2, the virus that causes COVID-19, had significant inflammation of a protein called cytokines in the cerebrospinal fluid. Within the brain, cytokines serve to send a signal to immune system cells to increase or decrease activity.

When those cytokines become inflamed and direct cells to overreact, microglia cells that consume cellular debris in the brain inflict increased damage to myelin, a fatty coating protecting the axon, or the arm of the neuron. In both COVID-19 patients and people who have chemo brain, the dismantling of myelin slows transmission of nerve signals, the researchers found.

Monje and her colleagues found in past studies that chemotherapy, like COVID-19 infection, affects the function of the brain's white matter, regions of the brain normally rich in well-insulated nerve fibers that quickly transmit signals from one place to another.

Chemo brain refers to people who have received chemotherapy and report being unable to remember certain pieces of information and having trouble with finishing tasks, concentration or learning new skills, according to the American Cancer Society.

Similarly, COVID-19 patients describe trouble with concentration, memory function and attention. In research published by Stanford Medicine one year into the pandemic, scientists concluded that "about one in four COVID-19 patients had cognitive symptoms that lingered at least two months, even after mild infections."

Symptoms of long COVID, or post-COVID-19 conditions, as defined by the Centers for Disease Control and Prevention, include difficulty thinking or concentrating, also known as "brain fog."

On top of its connection to chemo brain, the effects of COVID-19 brain fog also compare to other neurological conditions.

"The genes expressed in microglia after COVID-19 overlapped closely with those expressed by microglia in other disease contexts, including cognitive decline in aging and in neurological conditions such as Alzheimer's disease," according to a Stanford press release regarding the research.

In this most recent experiment, the researchers found that "even mild COVID can cause prominent inflammation in the brain that dysregulates brain cells and would be expected to contribute to cognitive impairment," they said.

With this newfound link between conditions and the pre-existing research on chemo brain, Monje hopes to use that knowledge to inform treatments for COVID-19 brain fog. Monje's team is already conducting research on medications that could alleviate brain fog after chemotherapy, and they plan to investigate whether these drugs are helpful after SARS-CoV-2 infection, according to the Stanford press release.

"The exciting message is that because the pathophysiology is so similar, the last couple of decades in cancer therapy-related research can guide us to treatments that may help COVID brain fog," Monje said.

Anthony Fernandez-Castaeda, postdoctoral scholar at Stanford University; Anna Geraghty, instructor of neurology at Stanford; Peiwen Lu, postdoctoral scholar at Yale University; and Yale graduate student Eric Song are the study's lead authors.