ABSTRACT
Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea.Copyright © Chuchalin A.G. et al., 2023.
ABSTRACT
Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase®) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea. © Chuchalin A.G. et al., 2023.
ABSTRACT
Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea.Copyright © Chuchalin A.G. et al., 2023.
ABSTRACT
One of the most likely and serious complications of the novel coronavirus infection (COVID-19) is pneumofibrosis, which can negatively affect the duration and quality of life of patients who have suffered from this disease. The appearance of fibrotic changes in COVID-19 is due to a number of pathological processes that occur in the lungs after the pathogen, the SARS- CoV-2 virus, enters there. First of all, an inflammatory response is triggered, which is mediated by macrophages and granulocytes, due to which the synthesis of pro-inflammatory cytokines, incl. IL-1, TNF, which are potent inducers of hyaluronic acid synthetase. There is a decrease in the content of fibrinolysis activators in the pulmonary endothelium, which contributes to the accumulation of fibrin in the vessels of the lungs. Fibrin can escape into the interstitial space and cause the formation of sclerosing alveolitis. The increasing defeat of pneumocytes favors the release of fibrin into the lumen of the alveoli, which causes the formation of hyaline membranes. The regulation of the fibrotic process involves immunocompetent cells, primarily CD4 + T-lymphocytes, which are capable of producing cytokines, chemokines and growth factors, and these, in turn, stimulate the proliferation and differentiation of fibroblasts, as well as their production of collagen. The more severe forms of infectious process can lead to the greater risk of developing fibrotic changes. Risk factors are a large area of lung damage, the use of artificial pulmonary ventilation, ARDS, fibrosis in anamnesis. An additional role in the pathomorphogenesis of pneumofibrosis is played by smoking, external inhalation effects (inhalation of organic and inorganic dust), gastroesophageal reflux, type II diabetes mellitus, genetic factors (familial idiopathic pulmonary fibrosis). The pathogenetic features of COVID-19 require administration of anti-fibrotic treatment. Bovhyaluronidazum azoximerum, a drug that is a conjugate of the proteolytic enzyme hyaluronidase, is considered as an antifibrotic agent. The treatment regimens with this drug recommended in the period of convalescence for patients who have undergone COVID-19 are given. © Chernyavskaya O.A., Osipov А.V., 2021.