ABSTRACT
ObjectivesTo identify putative COVID-19 treatments and identify the roles of immunomodulators and antivirals in disease management. DesignSystematic review. Data sourcesPubMed, bioRxiv.org and medRxiv.org were searched for studies suggestive of effective treatments for COVID-19. Additional studies were identified via a snowballing method applied to the references of retrieved papers as well as a subsequent targeted search for drug names. Review methodsInclusion criteria included any case series or randomised control trials in any language that were published from 18th December 2019 to 18th April 2020 and described COVID-19 treatment. Of an initial 2140 studies identified from the initial search, 29 studies were found to meet the inclusion criteria and included in this comprehensive systematic review. Results19 studies of antiviral treatments for COVID-19 have been reported and seven studies for immunomodulatory treatments. Six randomised controlled trials have been published with one positive trial for Hydroxychloroquine. This small study consisted of 31 patients though subsequent studies showed contradictory findings. All the remaining studies were observational studies, retrospective case reviews or non-randomised trials and these results are difficult to interpret due to methodological issues. ConclusionsTo date, an impressive number of studies have been performed in a short space of time, indicative of a resilient clinical trials infrastructure. However, there is a lack of high quality evidence to support any novel treatments for COVID-19 to be incorporated into the current standard of care. The majority of the studies of treatments for COVID-19 could only be found in pre-print servers. Future clinical reviews should therefore be Comprehensive Systematic Reviews involving pre-print studies to prevent potential unnecessary replications of clinical studies.
ABSTRACT
Hypertension and estrogen deficiency in women have been identified as significant risk factors for cerebrovasculardiseases. Hypertension causes excessive vascular stretch and contributes to the initiation of cellular injury in bloodvessels while estrogen has been demonstrated to exert beneficial protective effects on the vascular system. Although thespecific biological outcomes exerted by either excessive stretch or estrogen exposure are well established, the combinedbiochemical effects of both stimuli remain unclear. Therefore, this study was conducted for quantitative proteomics studyon human cerebral microvascular endothelial cells (HCMECs) subjected to 20% “pathological” cyclic stretch for aperiod of 18 hour in the presence or absence of 17β-estradiol by isobaric Taqs for Relative and Absolute Quantification.The results showed that only some proteins responded to 17β-estradiol (e.g., thioredoxin reductase-1), stretch (e.g., 14-3-3 protein epsilon or acidic leucine-rich nuclear phosphoprotein 32 family member B) and interestingly, some proteinsreturned to control pre-treatment levels when exposed to both (e.g., d-dopachrome decarboxylase, thrombospondin-1). Inaddition, HCMECs that exposed only to estrogen had a very similar proteomic profile (i.e., up-regulation of structural,cellular adhesion and proliferation proteins) as to those exposed to estrogen with 20% stretching for 18 hour, suggestingthat estrogen ablated the detrimental effects by the stretch alone. These findings sheds light on the molecular mechanismsby which the cerebrovascular protective actions of estrogen on HCMEC exposed to pathological levels of cyclic stretchwhich could provide a platform for future research in therapeutic approach.
