Scientists studying the persistent “brain fog” that plagues many people after a bout with COVID-19 are reporting, for the first time, abnormalities in the clear liquid surrounding the brain and spinal cord of several patients.
The discovery of elevated protein levels in the cerebrospinal fluid suggests the presence of inflammation, while unexpected antibodies may reveal an abnormally activated immune system, according to small study led by UCSF and published Tuesday in the journal Annals of Clinical and Translational Neurology.
“It’s possible that the immune system, stimulated by the virus, may be functioning in an unintended pathological way” even though the virus was no longer present, said Dr. Joanna Hellmuth, a brain expert at UCSF’s Coronavirus Neurocognitive Study and the study’s senior author.
Overall, the abnormalities also provide evidence to support what such patients have been insisting since the pandemic began: that their debilitating, post-COVID cognitive problems are real — not a matter of being tired or stressed, say the study’s authors.
“A lot of people have been told by doctors, friends or family that they’re crazy,” Hellmuth said. “We need to not dismiss people if we don’t know what’s going on.”
“Brain fog” is among the most common complaints of people suffering from long COVID, the mysterious array of unrelenting symptoms experienced by a subset of people infected by the coronavirus.
The cognitive complaints usually focus on “executive functions” — remembering recent events, recalling names and other details, concentration, speed of thought — all of which are supported by the brain’s frontal networks, said Hellmuth, noting that people can also experience such difficulties for reasons other than COVID.
Study participants with brain fog had an average of 2.5 cognitive risk factors — such as diabetes, high blood pressure or a history of alcohol use — while those without brain fog had less than one risk factor, on average.
The researchers — including those at New York’s Weill Cornell Medicine, as well as UCSF’s Alexandra Apple, Steven Deeks and Samuel Pleasure, among others — studied 17 participants who had had COVID an average of 10 months earlier but had never been hospitalized for it. All but four had persistent cognitive symptoms since becoming infected.
After performing a lumbar puncture in each volunteer, the researchers analyzed the cerebrospinal fluid that helps regulate blood flow to the brain, among other functions.
The four with no cognitive symptoms had normal cerebrospinal fluid.
But 10 of the remaining 13 participants showed elevated protein levels in the vital liquid, suggesting heightened inflammation and, in some cases, had antibodies indicating a potentially overactive immune system.
The findings are just one step in a long road toward understanding post-COVID brain fog, Hellmuth said, noting that the anomalies “may not be causing the cognitive changes” but are clearly associated with the condition.
Dr. Avindra Nath, clinical director of the National Institute of Neurological Disorders and Stroke, who was not involved in the study, said drawbacks include its small sample size and several unknowns, including whether the abnormalities will persist in all the patients or disappear in some, and what effect the underlying conditions had on the patients with brain fog.
“It is well known that any systemic infection can worsen an underlying condition and unmask it,” he said.
But Nath said the study’s strengths are that the researchers were able to document “the possibility that some of the (cognitive) manifestations may be immune mediated” — influenced by an immune response gone awry — among a group of non-hospitalized patients with mild COVID symptoms.
Dr. Jennifer Frontera, a neurologist specializing in brain injury at NYU Langone Health in New York, who is also unaffiliated with the study, called it interesting despite its small size and its reliance on self-reported symptoms.
“At the end of the day, I like what they’re doing. They’re looking at people in a very systematic fashion,” Frontera said. “As they continue this work and have a larger number of participants, I think they’ll be able to generate data that offers even more insight into the possible underlying mechanisms of post-COVID cognitive dysfunction.”
Cliff Morrison of Oakland has had persistent brain fog since being diagnosed with COVID in April 2020. A patient of Hellmuth’s who is enrolled in several UCSF studies of long COVID, Morrison doesn’t know if the researchers included his cerebrospinal fluid in their research. But he said he’s glad the scientists are on the case.
“It makes me more optimistic,” said Morrison, 70, whose forgetfulness led him to retire last week from his job as a health care administrator in Castro Valley after nearly two decades on the job. “It seems like the research is going slow, but we’ve been doing this for less than two years. This study has given me hope.”
COVID isn’t the only virus associated with post-infection cognitive problems. Others include HIV, coronaviruses such as SARS and MERS, Hepatitis C and Epstein-Barr.
Nanette Asimov is a San Francisco Chronicle staff writer. Email: nasimov@sfchronicle.com Twitter: @NanetteAsimov