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As coronavirus disease 2019 (COVID-19) and aging are both accompanied by cognitive decline, we hypothesized that COVID-19 might lead to molecular signatures similar to aging. We performed whole-transcriptome analysis of the frontal cortex, a critical area for cognitive function, in individuals with COVID-19, age-matched and sex-matched uninfected controls, and uninfected individuals with intensive care unit/ventilator treatment. Our findings indicate that COVID-19 is associated with molecular signatures of brain aging and emphasize the value of neurological follow-up in recovered individuals.