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2022 Neuropsychological Effects of COVID-19 in Older Adults from Health Disparity Populations (NAN)

COVID-Associated Cognitive Changes, Mood, and CSF Profiles in Older Adults

Are cognitive and mood symptoms of Long COVID associated with brain inflammation?

Joanna Hellmuth, M.D., M.H.S
University of California
San Francisco, CA - United States


Some individuals who contract SARS-CoV-2, the virus responsible for COVID-19, have continued to experience persistent respiratory, neurological, psychological and cardiac symptoms weeks to months after initial infection. This condition, referred to as “Long COVID,” is marked by the continuation of COVID-19 symptoms, or the emergence of new ones, after recovery from the initial phase of illness.

One common cognitive symptom experienced by individuals with Long COVID are changes in memory, function and behavior, including mood. Although the causes of these cognitive and mood changes are not well understood, immune cell response and brain inflammation has been shown to persist after SARS-CoV-2 infection and may contribute to other changes.

In preliminary studies, Dr. Joanna Hellmuth and colleagues suggest that baseline risk factors to cognitive impairment and biological markers (biomarkers) of inflammation may be more common in individuals who experience Long COVID cognitive changes. However, the relationship between risk factors, cognitive and mood symptoms, and inflammation in Long COVID is not well understood.

Research Plan

Dr. Hellmuth and colleagues will study cognitive and mood changes associated with Long COVID in older adults (60 years and older) recruited from the Coronavirus Neurocognitive Study (CNS). These individuals have recovered from SARS-CoV-2 infection, dividing them into those who report Long COVID and those that do not.

At an initial in-person visit, the researchers will characterize the details of COVID-19 illness, medical history, medications, cognitive changes, mood, and overall functioning to better understand the differences between those who have Long COVID and those that do not. At this initial appointment, the team will also collect blood samples and, in a subset of participants, cerebrospinal fluid (biological fluid surrounding the brain and spinal cord) samples to analyze biomarkers of inflammation and nerve cell damage. Dr. Hellmuth and team will follow up with participants with a phone call six months later to assess factors associated with symptom improvement.


The results may help shed light on whether inflammation is associated with cognitive and/or mood symptoms of Long COVID in older adults. The findings may help identify individuals who may be most at risk for these symptoms and inform future interventions for individuals with COVID-19.

The NeuroCOVID Grant Program was developed jointly with the Alzheimer's Association and the National Academy of Neuropsychology.

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