Severe COVID-19 has been associated with cognitive impairment and changes in the frontal cortex. In a study published in Nature Aging, Mavrikaki, Lee et al. performed RNA sequencing on frontal cortex samples from 21 individuals with severe COVID-19, 22 age- and sex-matched uninfected controls, and 9 uninfected people who had received intensive care or ventilator treatment. The authors found almost 7,000 differentially expressed genes (DEGs) in the patient samples compared to controls. Upregulated DEGs were enriched for genes involved in immune-related pathways, and downregulated DEGs were enriched for genes involved in synaptic activity, cognition and memory — a profile of transcriptional changes that resembles those previously observed in aging brains. Direct comparisons between frontal cortex samples from young and old individuals confirmed this overlap. Application of tumor necrosis factor, interferon-β or interferon-γ to cultured human primary neurons induced transcriptional changes similar to those seen in patients with severe COVID-19. As no SARS-CoV-2 RNA was detected in the patient samples, these data suggest that the transcriptomic changes in frontal cortex of patients with severe COVID-19 were due to neuroinflammatory processes rather than a direct effect of the virus.

Welberg, L. COVID-19 and brain aging. Nat Neurosci 26, 1 (2023). https://doi.org/10.1038/s41593-022-01249-5