MicroRNA 205-5p and COVID-19 adverse outcomes: Potential molecular biomarker and regulator of the immune response.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The uncontrolled systemic inflammatory response, resulting from the release of large amounts of pro-inflammatory cytokines, is the main mechanism behind severe acute respiratory syndrome and multiple organ failure, the two main causes of death in COVID-19. Epigenetic mechanisms, such as gene expression regulation by microRNAs (miRs), may be at the basis of the immunological changes associated with COVID-19. Therefore, the main objective of the study was to evaluate whether the expression of miRNAs upon hospital admission could predict the risk of fatal COVID-19. To evaluate the level of circulating miRNAs, we used serum samples of COVID-19 patients collected upon hospital admission. Screening of differentially expressed miRNAs in fatal COVID-19 was performed by miRNA-Seq and the validation of miRNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The Mann-Whitney test and receiver operating characteristic (ROC) curve were used to validate the miRNAs, whose potential signaling pathways and biological processes were identified through an in silico approach. A cohort of 100 COVID-19 patients was included in this study. By comparing the circulating levels of miRs between survivors and patients who died due to complications of the infection, we found that the expression of miR-205-5p was increased in those who died during hospitalization, and the expression of both miR-205-5p (area under the curve [AUC] = 0.62, 95% confidence interval [CI] = 0.5-0.7, P = 0.03) and miR-206 (AUC = 0.62, 95% CI = 0.5-0.7, P = 0.03) was increased in those who lately evolved to severe forms of the disease (AUC = 0.70, 95% CI = 0.6-0.8, P = 0.002)."In silico" analysis revealed that miR-205-5p has the potential to enhance the activation of NLPR3 inflammasome and to inhibit vascular endothelial growth factor (VEGF) pathways. Impaired innate immune response against SARS-CoV-2 may be explained by epigenetic mechanisms, which could form early biomarkers of adverse outcomes.

Self-perceived quality of life of primary antiphospholipid syndrome patients using vitamin K antagonist.

PURPOSE: Primary antiphospholipid syndrome (PAPS) is a chronic autoimmune disorder clinically characterized by thromboembolic events or obstetric complications. Prolonged anticoagulation therapy with vitamin K antagonists (VKA) is the treatment of choice for PAPS patients with thrombosis. However, the efficacy of VKA therapy depends on laboratory monitoring, dose adjustment, adequate lifestyle and adherence to treatment. Difficulties with VKA therapy can affect patients' self-perceived health related quality of life (HRQOL). This study aims to evaluate PAPS patients' HRQOL, therapy adherence and knowledge of treatment. METHODS: A general Medical Outcome Study Short Form-36 (SF-36) and the Duke Anticoagulation Satisfaction Scale (DASS) were used to access APS-patients self-perceived HRQOL. Treatment adherence was measured by the Treatment Measure Adhesion (TMA) - oral anticoagulant version instrument, and knowledge of VKA treatment was measured using the MedTake test. RESULTS: 66 PAPS patients using VKA were assessed. 63% of them were female; the mean age was 41.9 years old, approximately 60% had unprovoked venous thrombosis and one third of the patients had recurrent thrombotic events. The most impacted domain of DASS was "psychological impacts" and the factors associated to anticoagulation related poor HRQOL were: female sex, presence of arterial thrombosis and INR lability. Using the SF-36 instrument, PAPS-patients self-perceived HRQOL was poorer than that of the general Brazilian population and was associated with female sex and presence of cardiovascular risk factors. CONCLUSION: Despite the high adherence to treatment and knowledge of VKA therapy, self-perceived HRQOL is poor in patients with PAPS and is mainly affected by VKA therapy. Searching for better treatment options is warranted.