RESUMO
The sickle cell disease (SCD) population has been considered particularly vulnerable to viral pandemics since the emergence of H1N1 in 2009. In this sense, the advance of the COVID-19 pandemic from 2020 has brought this group of patients to the center of concern. However, scientific knowledge about the susceptibility of patients with SCD to a severe COVID-19 pandemic is still insufficient, and efforts to establish a general profile of the disease in these patients, remain inadequate. The present study, therefore, sought to characterize the case fatality rate and severity of COVID-19 in patients with SCD throughout the world. A systematic review of Pubmed/MEDLINE, Scopus, Cochrane Library, and Virtual Health Library databases through December 2021 was then performed. Subsequently, the primary and secondary outcomes were used in the meta-analysis in RStudio® software. Seventy-two studies were included with 6,011 SCD patients confirmed to have SARS-CoV-2 infection between mid-2020 and early 2022. The mean age of patients was 27 years. During this period, 218 deaths caused by COVID-19 were reported in the studied population, corresponding to an overall case fatality rate of 3%. In addition, 10% of patients with SCD were admitted to the ICU after complications caused by COVID-19, and 4% of them required invasive ventilatory support. In conclusion, the high fatality rate, intensive care unit admission and need for mechanical ventilation due to COVID-19 in young patients with SCD indicate that this population is at high risk for severe disease progression.
Assuntos
Anemia Falciforme , COVID-19 , Vírus da Influenza A Subtipo H1N1 , Humanos , Adulto , SARS-CoV-2 , Pandemias , Anemia Falciforme/complicaçõesRESUMO
The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt)/mechanistic target of rapamycin (mTOR) signaling pathway has been associated with several pathologies in the central nervous system (CNS), including epilepsy. There is evidence supporting the hypothesis that the PI3Kγ signaling pathway may mediate the powerful anticonvulsant properties associated with the cannabinoidergic system. This work aims to investigate if the anticonvulsant and neuroprotective effects of cannabidiol (CBD) are mediated by PI3Kγ. In vitro and in vivo experiments were performed on C57Bl/6 wild-type (WT) and PI3Kγ-/- mice. Behavioral seizures were induced by bilateral intra-hippocampal pilocarpine microinjection. Twenty-four hours after the first behavioral seizure, animals were perfused and their brains removed and processed, for histological analysis of neurodegeneration, microgliosis and astrocytosis. Primary cultures of hippocampal neurons were used for glutamate-induced cell death assay. CDB increased latency and reduced the severity of pilocarpine-induced behavioral seizures, as well as prevented postictal changes, such as neurodegeneration, microgliosis and astrocytosis, in WT animals, but not in PI3Kγ-/-. CBD in vivo effects were abolished by pharmacological inhibition of cannabinoid receptor or mTOR. In vitro, PI3Kγ inhibition or deficiency also changed CBD protection observed in glutamate-induced cell death assay. Thus, we suggest that the modulation of PI3K/mTOR signaling pathway is involved in the anticonvulsant and neuroprotective effects of CBD. These findings are important not only for the elucidation of the mechanisms of action of CBD, which are currently poorly understood, but also to allow the prediction of therapeutic and side effects, ensuring efficacy and safety in the treatment of patients with epilepsy.