Souradip Mallick, National Institute of Technology, Rourkela
In the last two decades, various coronavirus diseases have become a major public health issue, starting with the SARS-CoV pandemic in 2002 through 2003, then the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic in 2012, and current the COVID-19 pandemic. In all the cases, it has been reported that 20% of recovered patients had ongoing memory impairment. In the case of COVID-19, there are many side effects such as loss of taste or smell, stroke, delirium, diarrhea, and cognitive dysfunction also develops. This cognitive impairment due to coronavirus disease potentially leads to a surge in cases of Alzheimer’s-like dementia or other problems. These other problems can be various forms of neurocognitive impairment shortly. COVID-19 patients with dementia have a high mortality rate, and their health conditions gradually deteriorate. In a recent study among more than 236,000 COVID-19 survivors, it was observed that the patients who required hospitalization, ICU admission, had elevated risks of neurological and psychiatric disorders.
Though some claimed that SARS-CoV-2 is absent from the brain and cerebrospinal fluid (CSF) but it may directly infect the brain, potentially through the olfactory bulb. According to recent studies, SARS-CoV-2 spike protein can readily cross the blood-brain barrier (BBB) causing an inflammatory response within microvascular endothelial cells thereby cause BBB dysfunction. Multi-omics datasets for patients having COVID-19, such as bulk and single-cell transcriptomic, proteomic, and interactomic (protein-protein interactions [PPIs]) datasets were generated to identify the pathophysiological pathways of infection.
The invasion of SARS-CoV-2 was investigated at three different levels such as tissue, brain regions, and brain cell types. It has been observed that there was a low expression of ACE2,docking receptor of SARS-CoV-2 and TMPRSS2 in the brain and neurons. The other docking receptors BSG, NRP1, and FURIN had elevated expression in the endothelial cells in the prefrontal cortex region of both AD patients (those with Alzheimer’s-like dementia) and healthy controls compared to other brain cell types. This result showed that though ACE2 cannot target neurons, SARS-CoV-2 can enter the brain through the cerebral endothelium using receptors.
In Alzheimer’s-like dementia neuro-inflammation commonly occurs. The brain microvascular injury has a significant role in COVID-19-mediated cognitive impairment. NKTR, GSTM3, TGFB1, TNFRSF1B, SPP1, and CXCL10 genes were significantly altered in the CSF (cerebrospinal fluid) of COVID-19 patients. Network analysis showed that these genes were enriched in PPIs of immune-related gene products, such as ITGB1 and ARRB2. Moreover, the endothelial cells also have elevated expression of antiviral defense genes (LY6E, IFITM2, IFITM3, and IFNAR1). The PPI partners STAT3 and JAK1 combined with SARS-CoV-2 host factor datasets. The individuals with APOE E4/E4 had overall lower expression of antiviral defense genes compared to individuals with APOE E3/E3, suggesting a lack of expression of these genes and potentially elevated risk of SARS-CoV-2 infection. Human-induced pluripotent stem cell models had elevated susceptibility to SARS-CoV-2 infection in APOE E4/E4 brain cells. Hence there is significant mechanistic overlap between AD and COVID-19, centered on neuro-inflammation and microvascular injury. Dementia-like cognitive impairment is related to the complication of SARS-CoV-2 infection.
Also read: Understanding the importance of forensic odontology
References:
- Zhou, Y., Xu, J., Hou, Y. et al. Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment. Alz Res Therapy 13, 110 (2021). https://doi.org/10.1186/s13195-021-00850-3
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