“It’s well accepted that the brain is affected by the novel coronavirus, but most studies on long COVID have focused on older people who had severe disease,” said Michael L. Lipton, MD, PhD, co-principal investigator on the grant, Professor of Radiology and of Psychiatry and Behavioral Sciences and Associate Professor in the Dominick P. Purpura Department of Neuroscience at Einstein. “Our study is different because we have access to pre-pandemic brain imaging and in-depth cognitive assessments from hundreds of previously healthy, racially and ethnically diverse young men and women in their 20s and 30s who have participated in other Einstein studies.”

Dr. Lipton is also Associate Director of Einstein’s Gruss Magnetic Resonance Research Center and Medical Director of MRI Services at Montefiore Health System.

A “Natural History” of Brain Changes

The researchers will divide 140 study participants into three groups: 70 people who were never infected with SARS-CoV-2; 35 people who, based on laboratory tests, were infected but who were not symptomatic; and 35 people who were infected and had mild COVID-19 symptoms and did not require hospitalization. Participants will undergo physical and neurological examinations, cognitive and psychiatric assessments, and magnetic resonance imaging (MRI) tests. They will also provide blood samples at several points during the three-year study.

“By looking at participants’ blood serum and immune cells, we will attempt to identify the cellular mechanisms related to their immune response and determine their association with brain changes or cognitive issues,” said Johanna P. Daily, MD, MS, co–principal investigator on the grant, Professor of Medicine and of Microbiology & Immunology at Einstein and an Infectious Disease Physician at Montefiore Einstein.

The researchers also will study whether the stress of the pandemic itself contributed to changes in the brain or cognition in all study participants, whether or not they were infected. “We’re going to home in on things like loneliness, social support, mood, anxiety and changes in socioeconomic status,” said Dr. Lipton. “The goal is to tease out the effects of the pandemic from the effects of a SARS-CoV-2 infection.”

Dr. Lipton added that identifying subtle effects of SARS-CoV-2 on the brain that are undetectable by physicians or patients themselves may help clinicians predict what may be a looming public health issue. “SARS-CoV-2 infection may negatively affect current brain functioning and presage future neurodegeneration and dysfunction,” Dr. Lipton said. “Understanding the mechanisms and potentially developing targeted treatment could head off future problems.”

The grant, titled “Characterizing persistent subclinical neurobehavioral effects of COVID-19 in a diverse urban population,” is funded by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health (1R01NS123445).