A groundbreaking study conducted by Harvard Medical School and Brigham and Women’s Hospital in Boston has shed light on the potential impact of COVID-19 on cognitive function. The study focused on the role of long noncoding RNAs (lncRNAs), a class of RNA molecules that play a crucial role in gene expression regulation, in severe cases of the disease.
Using RNA-seq data from the frontal cortex of individuals with severe COVID-19 and uninfected controls, the researchers found significant dysregulation of both coding and noncoding RNAs, including various lncRNAs. These transcriptomic changes were distinct and clearly separated COVID-19 cases from the control group.
Of particular interest were two lncRNAs, LINC01007 and LINC01094, which showed expression patterns similar to those observed in the brains of aged individuals and Alzheimer’s Disease patients. This suggests a potential link between severe COVID-19 and cognitive decline. Other lncRNAs associated with brain aging and Alzheimer’s Disease were also implicated in the study, further supporting this connection.
Pathway analysis revealed that the dysregulated lncRNAs were involved in pathways associated with cognitive functions such as memory and learning. This finding strengthens the hypothesis that severe COVID-19 may have a direct impact on cognitive performance. The researchers validated their findings using quantitative real-time polymerase chain reaction (qRT-PCR), which confirmed the association between dysregulated lncRNAs and cognitive decline.
To assess the relevance of these findings to cognitive performance, the researchers analyzed cognitive and transcriptomic data from a separate cohort. The results showed that the dysregulated lncRNAs in severe COVID-19 were associated with poor cognitive performance. This association remained significant even when considering COVID-19 cases with a history of intensive care unit or ventilator treatment, suggesting that lncRNAs play an independent role in cognitive decline.
Considering the known link between inflammation and COVID-19-related neurological effects, the study also investigated the expression changes of lncRNAs in primary human neurons upon cytokine treatment. The researchers identified several lncRNAs that were differentially expressed in severe COVID-19 and poor cognition. They also discovered the potential regulatory role of antisense lncRNAs on inflammation-related protein-coding genes.
Overall, this study provides valuable insights into the relationship between severe COVID-19, cognitive decline, and dysregulated lncRNAs. The identified lncRNAs could be potential targets for therapeutic interventions aimed at mitigating cognitive deficits associated with the disease. Further research is needed to fully understand the molecular mechanisms underlying COVID-19-related neurological consequences and develop targeted treatments.
The findings of this study were published in the peer-reviewed journal Frontiers in Immunology.