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Objectives: We designed a cohort study to describe characteristics and outcomes of patients with coronavirus disease (COVID-19) admitted to the intensive care unit (ICU) in the largest public hospital in Sao Paulo, Brazil, as Latin America becomes the epicenter of the pandemic., Methods: This is the protocol for a study being conducted at an academic hospital in Brazil with 300 adult ICU beds dedicated to COVID-19 patients. We will include adult patients admitted to the ICU with suspected or confirmed COVID-19 during the study period. The main outcome is ICU survival at 28 days. Data will be collected prospectively and retrospectively by trained investigators from the hospital's electronic medical records, using an electronic data capture tool. We will collect data on demographics, comorbidities, severity of disease, and laboratorial test results at admission. Information on the need for advanced life support and ventilator parameters will be collected during ICU stay. Patients will be followed up for 28 days in the ICU and 60 days in the hospital. We will plot Kaplan-Meier curves to estimate ICU and hospital survival and perform survival analysis using the Cox proportional hazards model to identify the main risk factors for mortality. ClinicalTrials.gov: NCT04378582., Results: We expect to include a large sample of patients with COVID-19 admitted to the ICU and to be able to provide data on admission characteristics, use of advanced life support, ICU survival at 28 days, and hospital survival at 60 days., Conclusions: This study will provide epidemiological data about critically ill patients with COVID-19 in Brazil, which could inform health policy and resource allocation in low- and middle-income countries.

Schizophrenia is considered a debilitating neurodevelopmental psychiatric disorder and its pharmacotherapy remains problematic without recent major advances. The development of interventions able to prevent the emergence of schizophrenia would therefore represent an enormous progress. Here, we investigated whether treatment with cannabidiol (CBD - a compound of Cannabis sativa that presents an antipsychotic profile in animals and humans) during peri-adolescence would prevent schizophrenia-like behavioral abnormalities in an animal model of schizophrenia: the spontaneously hypertensive rat (SHR) strain. Wistar rats and SHRs were treated with vehicle or CBD from 30 to 60 post-natal days. In experiment 1, schizophrenia-like behaviors (locomotor activity, social interaction, prepulse inhibition of startle and contextual fear conditioning) were assessed on post-natal day 90. Side effects commonly associated with antipsychotic treatment were also evaluated: body weight gain and catalepsy throughout the treatment, and oral dyskinesia 48 h after treatment interruption and on post-natal day 90. In experiment 2, serum levels of triglycerides and glycemia were assessed on post-natal day 61. In experiment 3, levels of BDNF, monoamines, and their metabolites were evaluated on post-natal days 61 and 90 in the prefrontal cortex and striatum. Treatment with CBD prevented the emergence of SHRs' hyperlocomotor activity (a model for the positive symptoms of schizophrenia) and deficits in prepulse inhibition of startle and contextual fear conditioning (cognitive impairments). CBD did not induce any of the potential motor or metabolic side effects evaluated. Treatment with CBD increased the prefrontal cortex 5-HIAA/serotonin ratio and the levels of 5-HIAA on post-natal days 61 and 90, respectively. Our data provide pre-clinical evidence for a safe and beneficial effect of peripubertal and treatment with CBD on preventing positive and cognitive symptoms of schizophrenia, and suggest the involvement of the serotoninergic system on this effect.

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. In Parkinson's disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson's disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats. Male Wistar rats received four injections of CBD (0.5 or 5 mg/kg) or vehicle (days 2-5). On days 3 and 5, animals received also one injection of 1 mg/kg reserpine or vehicle. Locomotor activity, vacuous chewing movements, and catalepsy were assessed from day 1 to day 7. On days 8 and 9, we evaluated animals' performance on the plus-maze discriminative avoidance task, for learning/memory assessment. CBD (0.5 and 5 mg/kg) attenuated the increase in catalepsy behavior and in oral movements - but not the decrease in locomotion - induced by reserpine. CBD (0.5 mg/kg) also ameliorated the reserpine-induced memory deficit in the discriminative avoidance task. Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson's disease and tardive dyskinesia.

In schizophrenia (SCZ), higher angiotensin I-converting enzyme (ACE) levels have been reported in patient's blood and cerebrospinal fluid (CSF). Hereby, we propose to explore whether the ACE activity levels are associated to cognitive performance in SCZ. Seventy-two patients with SCZ or schizoaffective disorder diagnosis, and 69 healthy controls (HCs) underwent a cognitive battery with parallel collection of peripheral blood samples to measure ACE activity. Significant higher ACE activity levels were confirmed in the plasma of SCZ patients compared with HCs (Student's t=-5.216; P<0.001). ACE activity significantly correlated to Hopkins delayed recall measures (r=-0.247; P=0.004) and Hopkins total (r=-0.214; P=0.012). Subjects grouped as high ACE activity (above average) had worse performance compared with low ACE activity level group for Hopkins delayed recall measure, even after correction for clinical condition, age, gender and years of education (P=0.029). The adjusted R squared for this final model was 0.343. This result was evident only comparing extreme groups for ACE activity, when splitting the sample in three groups with similar number of subjects. To clarify this finding, we performed an evaluation of the cognitive performance of transgenic mice with three copies of ACE gene in novel object recognition (NOR) test, which showed that such animals presented impairment in NOR (P<0.05) compared with two copies of wild-type animals. The results observed in SCZ patients and animal model suggest both the association of ACE to cognitive deficits in SCZ. This finding may support the evaluation of novel treatment protocols and/or of innovative drugs for specific intervention of cognitive deficits in SCZ envisioning concomitant ACE activity and behavior evaluations., Competing Interests: AG received PhD fellowship from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), while AMV was a recipient of a fellowship from CNPq. MAS and CMY are recipients of a fellowship from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo). VO, VA, RAB and MAFH are all supported by FAPESP, CAPES and CNPq. MAFH is also the recipient of a fellowship from CNPq (311815/2012-0). RAB has also received lecture fees from Astra Zeneca, Bristol, Janssen and Lundbeck, with research grants from private companies such as Janssen, Eli Lilly, Lundbeck, Novartis and Roche, and Fundação Safra and Fundação ABADS. RAB is also a shareholder of Radiopharmacus Ltda and Biomolecular Technology Ltda. The remaining authors declare no conflict of interest.