LAUSR

[...]a "leaky" BBB may facilitate direct viral access to cortical neurons involved in the processing and integration of cognitive behaviors. Viruses may elicit CNS dysfunction via direct penetration of the BBB or they may enter the brain by hijacking the immune cell trafficking network (e.g., via circulating macrophages).11 Alternatively, active molecular agents generated by virus infection at a distant site (e.g., the lung) may have the capacity to modify the cognitive function of the host.12 CNS tissues may also serve as virus reservoirs, thereby promoting viral persistence and leading to chronic and/or recurrent cognitive dysfunction.12 Interestingly, the capacity to target the brain may be the result of virus-directed natural selection, as this process may ultimately promote the longevity and persistence of these pathogens. Bidirectional immune cell trafficking together with the development of virus-induced inflammation at the vascular endothelium may enhance normal immune cell trafficking to the brain, similar to a phenomenon that has been already reported in cases of Alzheimer's disease.13 Likewise, the virus-induced cytokine storm and enhanced immune cell trafficking may result in inflammation-associated psychiatric manifestations similar to those reported in cases of dementia, HIV infection, and post-cardiotomy delirium.11 Insights into the molecular basis of bidirectional trafficking and the limited protection provided by the selectively-penetrable BBB offer the opportunity for the development of efficacious novel therapeutics. [...]a full characterization of cognitive changes associated with SARS-CoV-2 and other severe virus infections will be critical for the diagnosis, prognosis, and plans for long-term care of these patients.