In this June 9, 2021 article, researchers at the Cleveland Clinic found possible explanations for the observation in the UK and elsewhere that people with ApoE 4/4 are more at risk from COVID-19.
We found significant network-based relationships between COVID-19 and neuroinflammation and brain microvascular injury pathways and processes which are implicated in AD. We also detected aberrant expression of AD biomarkers in the cerebrospinal fluid and blood of patients with COVID-19. While transcriptomic analyses showed relatively low expression of SARS-CoV-2 entry factors in human brain, neuroinflammatory changes were pronounced. In addition, single-nucleus transcriptomic analyses showed that expression of SARS-CoV-2 host factors (BSG and FURIN) and antiviral defense genes (LY6E, IFITM2, IFITM3, and IFNAR1) was elevated in brain endothelial cells of AD patients and healthy controls relative to neurons and other cell types, suggesting a possible role for brain microvascular injury in COVID-19-mediated cognitive impairment. Overall, individuals with the AD risk allele APOE E4/E4 displayed reduced expression of antiviral defense genes compared to APOE E3/E3 individuals.
More detail for those interested:
In this study, we investigated COVID-19-associated neurological manifestations using both network medicine methodologies and bulk/single-cell/single-nuclei transcriptomic data analyses. We identified strong shared neuroinflammatory responses between COVID-19 and AD. Several AD markers (CXCL10, TNFRSF1B, SPP1, TGFB1, GSTM3, and NKTR) have significantly altered expression in COVID-19 patients. Low expression levels of SARS-CoV-2 entry factors were found in human brains, indicating low possibility of direct brain damage by the virus. Transcriptomic analyses showed elevated expression levels of SARS-CoV-2 host factors (BSG and FURIN) and antiviral defense genes (LY6E, IFITM2, IFITM3, and IFNAR1) in brain endothelial cells compared to other cell types, suggesting possible brain microvascular injury by SARS-CoV-2 infection. In addition, individuals with APOE E4/E4 may have increased risk of SARS-CoV-2 infection by an overall lower expression of antiviral defense genes (LY6E, IFITM2, IFITM3, and IFNAR1) compared to individuals with APOE E3/E3. Altogether, these results can improve our understanding of COVID-19-associated neurological manifestations and provide guidance for future risk management of potential cognitive impairment by SARS-CoV-2 infection. Our findings could lay the foundation for future research that ultimately leads to testable and measurable serum biomarkers that could identify patients at highest risk of neurological complications with COVID-19.
Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment