Direct and indirect impact of SARS-CoV-2 on the brain

Although COVID-19 is mostly a pulmonary disease, it is now well accepted that it can cause a much broader spectrum of signs and symptoms and affect many other organs and tissue. From mild anosmia to severe ischemic stroke, the impact of SARS-CoV-2 on the central nervous system is still a great challenge to scientists and health care practitioners. Besides the acute and severe neurological problems described, as encephalopathies, leptomeningitis, and stroke, after 2 years of pandemic, the chronic impact observed during long-COVID or the post-acute sequelae of COVID-19 (PASC) greatly intrigues scientists worldwide. Strikingly, even asymptomatic, and mild diseased patients may evolve with important neurological and psychiatric symptoms, as confusion, memory loss, cognitive decline, chronic fatigue, associated or not with anxiety and depression. Thus, the knowledge on the correlation between COVID-19 and the central nervous system is of great relevance. In this sense, here we discuss some important mechanisms obtained from in vitro and in vivo investigation regarding how SARS-CoV-2 impacts the brain and its cells and function.