Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.

Schizophrenia Outside the Brain.

Schizophrenia is a multifactorial mental disorder, characterized by positive symptoms (delusions, hallucinations), negative symptoms (anhedonia, social withdraw), and cognitive symptoms (impairment of memory, learning, and executive functions). Despite the classic symptoms being related to the central nervous system, schizophrenia has been described by recent studies as a systemic disease, affecting other organs, tissues, and systems out of the brain. In this chapter, we summarize the main tissues and systems found affected in schizophrenic patients, both before and after antipsychotic administration. We offer an overview of the recent findings in the field about musculoskeletal system, metabolism, and immune system dysfunctions found in patients as well in models in vitro. We also discuss some of the side effects of certain antipsychotics often related to increased risk of comorbidities in patients with schizophrenia during the treatment.