ABSTRACT
The efficacy of melatonin in the treatment of patients with coronavirus 2019 (COVID-19) is controversial. This review has summarized the evidence on the efficacy of oral melatonin compared to placebo in patients with mild to moderate COVID-19 infection. We searched four international online databases and all randomized clinical trials (RCTs) that investigated the effects of melatonin compared with the placebo on clinical outcomes, including mortality, discharge time, O2 saturation (SaO2), and c-reactive protein (CRP) levels in patients with COVID-19 infection, were included. The standard random-effects model with hybrid continuity correction was used to pool the risk ratio (RR), weighted mean difference (WMD), and the I2 index to assess the heterogeneity. A total of 272 patients from five RCTs were included. Our meta-analysis showed melatonin compared to placebo, decreased discharge time (WMD=-0.93 days;95% confidence interval [CI]:-2.94 to 1.07, P=0.36;I2=56.78%) and the risk of mortality (RR=0.72;95% CI:0.25 to 2.13, P=0.56;I2=0.0%) in COVID-19 patients. Melatonin intake compared to placebo significantly increased SaO2 (WMD=1.38%;95% CI:0.09 to 2.68, P=0.04;I2=49.82%) and decreased the CRP levels (WMD=-7.24 mg/l;95% CI:-11.28 to-3.21, P<0.001) in a sensitivity analysis. Our findings showed the efficacy of melatonin compared to placebo in patients with mild to moderate COVID-19 infection. [GMJ.2022;11:e2562] DOI:10.31661/gmj.v11i.2562
ABSTRACT
Coronavirus infection is a clinical syndrome caused by a mutational RNA virus (SARS-CoV-2). In severe cases, it is characterized by the development of a “cytokine storm”. The latter leads to the multiple organ dysfunction, ARDS and causes high mortality. To suppress the cytokine aggression in patients with severe COVID-19, the drug suppression is recommended;however, the use of hemosorption can be pathogenetically justified as an alternative method. The aim of the study was to assess the effectiveness of hemosorption using the hemosorbent “Hemo-Proteazosorb” in the severe COVID-19 infection course in comparison to the drug suppression with tocilizumab. We studied the clinical and laboratory parameters of 88 patients who were treated at the anesthesiology and intensive care department. All patients were divided into 2 groups: Hemo-Proteazosorb (п = 53) and Tocilizumab (п = 33). Against the background of hemosorption using the Hemo-Proteazosorb sorbent, statistically the level of procalcitonin, C-reactive protein, leukocytes, fibrinogen, D-dimers significantly decreases, the number of lymphocytes increases, as well as the respiratory index earlier grows in comparison with the group receiving tocilizumab therapy. The study found that the use of hemosorption through the domestic sorbent “Hemo-Proteazosorb” has a number of advantages over the drug suppression of the “cytokine storm” with tocilizumab due to the more pronounced effects of immunomodulation, improvement of the oxygen transport function of blood, its rheological properties and the possibility of effective use in persons with viral bacterial infection.
ABSTRACT
The novel coronavirus (2019-nCoV/SARS-CoV-2) causes respiratory symptoms including a substantial pulmonary dysfunction with worsening arterial hypoxemia (low blood oxygenation), eventually leading to acute respiratory distress syndrome (ARDS). The impact of the viral infection on blood oxygenation and other elements of oxygen homeostasis, such as oxygen sensing and respiratory mitochondrial mechanisms, are not well understood. As a step toward understanding these mechanisms in the context of COVID-19, recent experiments revealed contradictory data on the impact of COVID-19 infection on red blood cells (RBCs) oxygenation parameters. However, structural protein damage and membrane lipid remodeling in RBCs from COVID-19 patients that may impact RBC function have been reported. Moreover, COVID-19 infection could potentially disrupt one, if not all, of the other major pathways of homeostasis. Understanding the nature of the crosstalk among normal homeostatic pathways; oxygen carrying, oxygen sensing (i.e., hypoxia inducible factor, HIF) proteins, and the mitochondrial respiratory machinery may provide a target for therapeutic interventions.
ABSTRACT
The transport of oxygen between blood and tissue is limited by blood's capillary transit time, understood as the time available for diffusion exchange before blood returns to the heart. If all capillaries contribute equally to tissue oxygenation at all times, this physical limitation would render vasodilation and increased blood flow insufficient means to meet increased metabolic demands in the heart, muscle, and other organs. In 1920, Danish physiologist August Krogh was awarded the Nobel Prize in Physiology or Medicine for his mathematical and quantitative, experimental demonstration of a solution to this conceptual problem: capillary recruitment, the active opening of previously closed capillaries to meet metabolic demands. Today, capillary recruitment is still mentioned in textbooks. When we suspect symptoms might represent hypoxia of a vascular origin, however, we search for relevant, flow-limiting conditions in our patients and rarely ascribe hypoxia or hypoxemia to short capillary transit times. This review describes how natural changes in capillary transit-time heterogeneity (CTH) and capillary hematocrit (HCT) across open capillaries during blood flow increases can account for a match of oxygen availability to metabolic demands in normal tissue. CTH and HCT depend on a number of factors: on blood properties, including plasma viscosity, the number, size, and deformability of blood cells, and blood cell interactions with capillary endothelium; on anatomical factors including glycocalyx, endothelial cells, basement membrane, and pericytes that affect the capillary diameter; and on any external compression. The review describes how risk factor- and disease-related changes in CTH and HCT interfere with flow-metabolism coupling and tissue oxygenation and discusses whether such capillary dysfunction contributes to vascular disease pathology.