Severe COVID-19 induces molecular signatures of aging in the human brain.
Maria MavrikakiJonathan D LeeIsaac H SolomonFrank J SlackPublished in: medRxiv : the preprint server for health sciences (2021)
Coronavirus disease 2019 (COVID-19) is predominantly an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and remains a significant threat to public health. COVID-19 is accompanied by neurological symptoms and cognitive decline, but the molecular mechanisms underlying this effect remain unclear. As aging induces distinct molecular signatures in the brain associated with cognitive decline in healthy populations, we hypothesized that COVID-19 may induce molecular signatures of aging. Here, we performed whole transcriptomic analysis of human frontal cortex, a critical area for cognitive function, in 12 COVID-19 cases and age- and sex-matched uninfected controls. COVID-19 induces profound changes in gene expression, despite the absence of detectable virus in brain tissue. Pathway analysis shows downregulation of genes involved in synaptic function and cognition and upregulation of genes involved in immune processes. Comparison with five independent transcriptomic datasets of aging human frontal cortex reveals striking similarities between aged individuals and severe COVID-19 patients. Critically, individuals below 65 years of age exhibit profound transcriptomic changes not observed among older individuals in our patient cohort. Our data indicate that severe COVID-19 induces molecular signatures of aging in the human brain and emphasize the value of neurological follow-up in recovered individuals.
Keyphrases
- sars cov
- coronavirus disease
- respiratory syndrome coronavirus
- cognitive decline
- public health
- gene expression
- mild cognitive impairment
- functional connectivity
- endothelial cells
- single cell
- resting state
- genome wide
- white matter
- early onset
- hiv infected
- autism spectrum disorder
- dna methylation
- rna seq
- big data
- cell proliferation
- drug induced
- working memory
- liver failure
- single molecule
- artificial intelligence
- multiple sclerosis
- blood brain barrier
- pluripotent stem cells
- deep learning
- acute respiratory distress syndrome
- aortic dissection
- genetic diversity