In 2020, a novel Coronavirus, Severe Acute Respiratory Syndrome-Covid-2 (SARS-CoV-2), spread globally to provoke a pandemic that infected over 750 million people. The associated disorder, Coronavirus-19 (COVID-19), has caused at least 7 million deaths and around a hundred million people have developed a variable yet sometimes incapacitating condition called Long Covid. This multi-organ syndrome, often referred to as “Brain Fog”, encompasses symptoms of extreme fatigue, anxiety, poor sleep and, most prominently, cognitive impairment. Long Covid emerges three or more months after SARS-CoV-2 infection and bears a marked resemblance to the suite of neurological symptoms that evolves several years after infection with Human Immunodeficiency Virus (HIV). Accordingly, by analogy to “HIV Associated Neurological Disorder” (HAND), the acronym,” SAND” is proposed for SARS-CoV-2 Associated Neurological Disorder. Mimicking HIV infection/HAND, SARS-CoV-2 infection/SAND is on a collision course with aging, leading to their mutual aggravation and an increased risk of disorders like Alzheimer’s and Parkinson’s disease. In contrast to HIV, where the virus crosses the blood-brain-barrier in T-lymphocytes and monocytes to infect microglia and other cell types, there is little evidence that SARS-CoV-2 enters the brain. Nonetheless, in addition to the indirect effects of a somatic hyper-inflammation (“cytokine storm”) and the disruption of blood- and CSF-brain barriers, SARS-CoV-2-encoded S1 Spike protein and other virally-encoded proteins enter the brain to directly interfere with cerebral function. Microglia and astrocytes adopt a pro-inflammatory phenotype, neurotoxic proteins accumulate, mitochondrial energy generation declines, and synaptic transmission is perturbed. These findings for SAND mirror observations seen with aging and dementia. A broad-based programme of “R and D”, healthcare and social support would appear desirable to better understand the complex set of interacting mechanisms underlying SAND, to prevent its onset, to alleviate the debilitating symptoms, and to improve our readiness for countering the impact of those novel, brain-damaging viruses that will inevitably arise in the future.
