ABSTRACT
The COVID-19 mortality is associated with an increase in interleukin-6 (IL-6) levels. Levilimab is an anti-IL-6 receptor antibody with proven clinical efficacy in patients with severe COVID-19. The aim of the study was to assess the association of COVID-19 severity and levilimab effectiveness with IL-6 levels and to explore the potential for using levilimab in other conditions accompanied by cytokine release syndrome. Material(s) and Method(s): the subgroup analysis was based on the data of COVID patients with known baseline IL-6 levels from the CORONA clinical study. Subgroups were formed according to baseline IL-6 levels: <=5 pg/mL (normal) and >5 pg/mL (elevated). The subgroup analysis included descriptive statistics of the patients and time courses of their clinical and laboratory findings (at screening, on the day of investigational product administration, and further until day 14). In order to compare the percentages of patients who had required rescue therapy, the authors used Fisher's exact test. Result(s): the subgroup analysis included 91 patients (47 from the levilimab group and 44 from the placebo group). At baseline, the authors observed elevated levels of IL-6 in 31/47 (66%) subjects in the levilimab group and 29/44 (48.4%) subjects in the placebo group. The subjects with elevated IL-6 demonstrated more pronounced clinical signs of pneumonia and abnormalities in inflammatory markers. Elevated baseline IL-6 levels were associated with the need for rescue therapy (OR=3.714;95% CI: 1.317-9.747;p=0.0183);this association was stronger in the placebo group (OR=8.889;95% CI: 2.098-33.31;p=0.0036). Also, the placebo group showed long-term abnormalities in the clinical and laboratory findings. Conclusion(s): IL-6 is one of the key elements in the pathogenesis of cytokine release syndrome related to COVID-19 and other conditions. Elevated IL-6 levels are associated with the severity of COVID-19. Inhibition of IL-6 receptors by levilimab leads to clinical improvement in patients with severe COVID-19, suggesting the effectiveness of levilimab in pathogenesis-oriented therapy for cytokine release syndrome of other aetiologies.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.
ABSTRACT
The COVID-19 mortality is associated with an increase in interleukin-6 (IL-6) levels. Levilimab is an anti–IL-6 receptor antibody with proven clinical efficacy in patients with severe COVID-19. The aim of the study was to assess the association of COVID-19 severity and levilimab effectiveness with IL-6 levels and to explore the potential for using levilimab in other conditions accompanied by cytokine release syndrome. Materials and methods: the subgroup analysis was based on the data of COVID patients with known baseline IL-6 levels from the CORONA clinical study. Subgroups were formed according to baseline IL-6 levels: ≤5 pg/mL (normal) and >5 pg/mL (elevated). The subgroup analysis included descriptive statistics of the patients and time courses of their clinical and laboratory findings (at screening, on the day of investigational product administration, and further until day 14). In order to compare the percentages of patients who had required rescue therapy, the authors used Fisher's exact test. Results: the subgroup analysis included 91 patients (47 from the levilimab group and 44 from the placebo group). At baseline, the authors observed elevated levels of IL-6 in 31/47 (66%) subjects in the levilimab group and 29/44 (48.4%) subjects in the placebo group. The subjects with elevated IL-6 demonstrated more pronounced clinical signs of pneumonia and abnormalities in inflammatory markers. Elevated baseline IL-6 levels were associated with the need for rescue therapy (OR=3.714;95% CI: 1.317–9.747;p=0.0183);this association was stronger in the placebo group (OR=8.889;95% CI: 2.098–33.31;p=0.0036). Also, the placebo group showed long-term abnormalities in the clinical and laboratory findings. Conclusions: IL-6 is one of the key elements in the pathogenesis of cytokine release syndrome related to COVID-19 and other conditions. Elevated IL-6 levels are associated with the severity of COVID-19. Inhibition of IL-6 receptors by levilimab leads to clinical improvement in patients with severe COVID-19, suggesting the effectiveness of levilimab in pathogenesis-oriented therapy for cytokine release syndrome of other aetiologies.
ABSTRACT
In connection with the COVID-19 pandemic, there is an urgent need for disinfecting devices that can be used both indoors and in transport. Currently, the most common of these devices are ultraviolet (UV) germicidal lamps. However, they have significant disadvantages, such as short service life, presence of mercury, lack of flexible control, large dimensions, etc. The paper analyzes the sources of UV radiation to find an alternative to UV lamps. Although these elements currently have low efficiency and high cost, etc., it is proposed to use UVC LEDs as a UV source. Due to the COVID-19 pandemic and the general interest in the fight against viruses, as well as the ban on the use of mercury, investments have been attracted in the development of UVC LEDs, which will make them competitive in the future compared to germicidal lamps both in cost and efficiency. The paper presents a disinfection device developed on the basis of UVC LEDs. The principle of operation is described;the control system, the drawing, and the design of the UVC LED-based disinfection device are presented. Due to the described limitations of UVC LEDs, this design can be used for disinfection of small surface areas where frequent on/off switching is required and high power is not required.
ABSTRACT
Background: Levilimab (LVL) is a novel anti-IL6Rmonoclonal antibody against IL6Rα. Cytokine release syndrome plays the key role in the pathogenesis of a range of life-threatening conditions including the acute respiratory distress syndrome in severely ill COVID-19 patients. Thus, the use of LVL could be considered as anti-cytokine therapy with a potency to prevent the complications and progression of respiratory failure in COVID-19. Objectives: We analyzed the changes in the serum concentrations of inflammatory markers (Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and IL-6) in patients treated with LVL or placebo as part of a phase III multicenter randomized double-blind placebo-controlled adaptive-design CORONA clinical study aimed to evaluate the efficacy and safety of LVL in subjects with severe COVID-19 (NCT04397562). Methods: A total of 217 patients were enrolled in the study, 206 patients were randomized, and 204 patients received the investigational product (IP, LVL or placebo). Study included men and non-pregnant women aged ≥18 years, hospitalized for severe COVID-19 pneumonia, receiving standard therapy according to the national guidelines. Patients with acute respiratory failure with the need in invasive respiratory support, septic shock, multiple organ failure or life expectancy less than 24 hours could not participate in the study. The use of other monoclonal antibodies and glucocorticoids for the treatment of COVID-19 were not allowed. Subjects were stratified according to the CRP level (CRP ≤ 7 mg/L;CRP ≥ 7 mg/L) and then randomized (1:1) into 2 groups to receive LVL 324 mg or placebo. LVL/ placebo were administered as a single subcutaneous injection, investigator and patients were unaware of the received therapy. Among secondary endpoints of the study changes from baseline in ESR, CRP and IL-6 concentrations were assessed. CRP level and ESR were measured before the IP administration and on Days 3, 5, 7, 14, 21, 29 and 30. Blood samples for the measurement of IL-6 concentration were obtained before the IP administration and then every day for 2 weeks after administration. Results: We observed the pronounced decrease of ESR in LVL group compared to Placebo group. The difference was statistically significant on Days 3 and 7: the median ESR change from baseline was -3 mm/h and +3 mm/h on Day 3, -11 mm/h and -3.1 mm/h on Day 7, in LVL and Placebo groups, respectively (p=0.0319 and p=0.0110, Days 3 and 7). The statistically significant difference in the change of CRP level was detected between the groups on Day 3: -26.6±41.9 mg/L and -19.2±58.2 mg/L in LVL and Placebo groups, respectively (p=0.0241). Numerically the same dynamics of ESR and CRP was observed over entire study period. The dynamics of IL-6 serum concentrations in LVL and Placebo groups was strikingly different. After LVL administration we detected the rapid significant increase in IL-6 concentration due to IL-6 receptors inhibition. Maximum change from baseline was observed on Day 3 (+91.9±117.7 pg/mL), on Day 14 the value was +31.9±62.7 pg/mL. In the Placebo group, the IL-6 concentration increased slightly until Day 4 (+5,1±76,5 pg/mL), and then decreased significantly (-39.2±55.1 pg/mL on Day 14) due to clinical improvement in this group. Conclusion: The significant differences in the dynamics of ESR, CRP and IL-6 after LVL administration compared to placebo confirmed the pharmacodynamic effect and its potency to prevent the excessive release of inflammatory substances in severely ill COVID-19 patients.
ABSTRACT
The new Coronavirus pandemic has exposed the healthcare professionals to a higher risk of morbidity and mortality. In order to protect the medical personnel, the patients and also to reduce the economic burden set upon the medical systems from around the world, the imaging techniques must be applied only in situations that can improve the therapeutic management. This article intends to analyse the existing recommendations in the medical journals regarding the cardiac imaging techniques during this pandemic period. The article also tries to summarize the main indications of those imaging techniques as well as highlighting the protective measures taken by the medical personnel during patient care.