Fig. 1.

Schematic representation of adaptive and maladaptive sickness behavioral responses. Elevated cytokine levels, resulting from various potential triggers, including SARS-COV-2 virus, act as neuromodulators informing the hypothalamus about an inflammatory stressor. The hypothalamus orchestrates adaptive biological responses to restore homeostasis, engendering sickness behavior. Therefore, both an exaggerated systemic inflammation in a healthy brain (e.g., COVID-19-associated cytokine storm) or a susceptible brain confronted with a relatively mild inflammatory stimulus (e.g., urinary tract infection in the elderly) may be sufficient to result in a disproportionate cytokine-mediated neuroinflammation, leading to encephalopathy.