COVID-19 exhibits a wide spectrum of clinical manifestations and long-term health implications, including cognitive decline following recovery from the infection. Recent studies have uncovered the role of SARS-CoV-2 infection in inducing neuroinflammation in individuals with long COVID syndrome.
Furthermore recent studies have shown having infection of COVID-19 doubles the risk of developing a new diagnosis of AD in the following year after infection in elderly people compared to non-infected controls.
The neuropathology of AD is described as the presence of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles (NFTs). Although these features are widely used to diagnose AD, they also occur in healthy ageing; furthermore, it has been seen that the loads of Aβ plaques and NFTs don’t correlate with cognitive performance. However, research has shown that neuroinflammation plays an important role in neurodegeneration.
Hence, we hypothesised that individuals suffering from long COVID-19 syndrome may exhibit inflammatory transcriptomic signatures akin to those seen in AD. Such similarities in inflammatory profiles could potentially lead to cognitive decline among long COVID-19 patients, primarily through neuroinflammation-induced neurodegeneration. This potential association raises significant public health concerns, as those infected during the pandemic may face an increased risk of developing more severe neurodegenerative conditions in the years ahead.
To investigate this hypothesis, we analyse the inflammatory transcriptomic profiles within the cerebral cortex using single-cell RNA sequencing (scRNAseq) data from both AD and COVID-19 donors. We also assess the overlapping heritability of the gene programs that are unregulated in both conditions and finally, we compare this to the heritability of statistically significant GWAS summary statistics.
Our results show evidence that the most relevant celltype displaying more statistically significant differentiated genes in contrast to healthy controls in AD and COVID-19, interestingly these expression patterns seen in severe COVID-19 have been reported as markers in early stage AD.