Fig. 1.

The possible interplay between liver and brain dysfunctions in COVID-19. Patients with COVID-19 often present liver damage, but it is currently unclear whether this is a direct consequence of SARS-CoV-2 infection or secondary to other systemic events. The liver is able to respond to and participate in the inflammatory response caused by SARS-CoV-2. In addition, liver damage can impair ammonia metabolism, increasing the circulating concentrations of this neurotoxic metabolite. Neurological symptoms frequently occur in COVID-19 patients, but the possibility of neuroinvasion by SARS-CoV-2 is also under investigation. However, the harmful effects of peripheral inflammatory mediators and ammonia on astrocyte functions are well established and are known to trigger morphological and neurochemical changes in these cells, which actively participate in the pathophysiology of encephalopathy. Colored circles represent inflammatory mediators, acute phase response proteins and ammonia, and the circle box displays astrocyte activation promoted by these molecules.