COVID-19 Pandemic - A Narrative Review of the Potential Roles of Chloroquine and Hydroxychloroquine.

BACKGROUND: Chloroquine (CQ) and hydroxychloroquine (HCQ) are old drugs used against malaria, rheumatism, inflammation in the joints, lupus, among others. These drugs showed positive results in preliminary scientific research for treatment of the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Since the studies with CQ and HCQ are initial with small patient populations, it is not yet known whether there are adverse effects from the use of CQ and HCQ for patients infected with the coronavirus. OBJECTIVES: The aim of this study was to evaluate the evidence regarding the efficacy and safety of CQ and HCQ used against viral infection caused by SARS-CoV-2. STUDY DESIGN: This is a narrative review of the traditional prescriptions of CQ and HCQ efficacy and adverse effects as well as their employment for coronavirus disease 2019 (COVID-19). SETTING: In vitro and clinical studies comparing the antiviral efficacy and adverse effect profile of CQ and HCQ against COVID-19 in adult patients were evaluated. METHODS: A systemic search of reviews, including in vitro and clinical trial studies in English focusing on CQ and HCQ effects and adverse effects against COVID-19 in the adult patient population from PubMed was performed. It included studies reporting chloroquine and hydroxychloroquine effects and adverse effects against COVID-19. RESULTS: A total of 42 articles published between 2004 and April 2020 were reviewed for therapeutic use of CQ and HCQ. Both these drugs showed a significant in vitro potential against coronavirus. Many studies for clinical use of CQ and HCQ showed that patients presented adverse reactions on high doses. LIMITATIONS: Clinical studies have some methodology shortcomings, such as lack of information about the treatment and small number of experimental patients, leading to a misinterpretation of the data. Besides, there are few clinical studies with a limited sample size. Moreover, most of them did not present control groups, and some patients had died during these protocols. DISCUSSION: Despite both CQ and HCQ in vitro antiviral evidence, clinically, both drugs, either alone or combined with other medications, may increase the risk of cardiac arrhythmias, leading to cardiac arrest and sudden death. Besides, a lot of uncertainty still remains, such as starting administration period, dose prescribed, length of treatment, patients' condition, concomitant drug use, among others. CONCLUSION: From the studies reviewed, it is not possible to state the precise efficacy and safety of CQ and HCQ use in the treatment of COVID-19 at any time in the course of the disease. Future studies are warranted.

Environmental tobacco smoke in the early postnatal period induces impairment in brain myelination.

Environmental tobacco smoke (ETS) is associated with high morbidity and mortality, mainly in children. However, few studies focus on the brain development effects of ETS exposure. Myelination mainly occurs in the early years of life in humans and the first three postnatal weeks in rodents and is sensitive to xenobiotics exposure. This study investigated the effects of early postnatal ETS exposure on myelination. BALB/c mice were exposed to ETS generated from 3R4F reference research cigarettes from the third to the fourteenth days of life. The myelination of nerve fibers in the optic nerve by morphometric analysis and the levels of Olig1 and myelin basic protein (MBP) were evaluated in the cerebellum, diencephalon, telencephalon, and brainstem in infancy, adolescence, and adulthood. Infant mice exposed to ETS showed a decrease in the percentage of myelinated fibers in the optic nerve, compared with controls. ETS induced a decrease in Olig1 protein levels in the cerebellum and brainstem and an increase in MBP levels in the cerebellum at infant. It was also found a decrease in MBP levels in the telencephalon and brainstem at adolescence and in the cerebellum and diencephalon at adulthood. The present study demonstrates that exposure to ETS, in a critical phase of development, affects the percentage of myelinated fibers and myelin-specific proteins in infant mice. Although we did not observe differences in the morphological analysis in adolescence and adulthood, there was a decrease in MBP levels in distinctive brain regions suggesting a delayed effect in adolescence and adulthood.