ABSTRACT
The pathophysiology of long-COVID sequelae in the general population of SARS-CoV-2-infected patients has been shown to be strongly influenced by oxidative stress. However, the potential role of oxidative stress in the development of long-COVID sequelae in hemodialysis patients (HD) has never been investigated. The present study aimed to evaluate the oxidative status of HD patients 3.5 months after SARS-CoV-2 infection in relation to the presence of long-COVID sequelae and the severity of the acute phase COVID-19. Methods. This cross-sectional cohort study included 63 HD patients with a median age of 55 (43-62.5) years and a dialysis vintage of 42 (25-73) months who had been infected with COVID-19 at least 3 months before recruitment. Patients were divided into two groups according to the occurrence of long-COVID sequelae: Group 1 included 31 (49.2%) HD patients with sequelae, while Group 2 included 32 (50.8%) fully recovered individuals. At 3.5 (3.2-4.6) months after the acute phase of COVID-19, malondialdehyde (MDA) and erythrocyte levels (MDAe), sulfhydryl groups (SH -groups), serum catalase activity, transferrin, and ceruloplasmin were measured. A comparison of the obtained data was performed using the Student's test or the Mann-Whitney test according to the data distribution. A correlation was evaluated with the Spearman test. Results. HD patients with persistent long-COVID sequelae had significantly higher concentrations of MDAs (p = 0.002), MDAe (p = 0.0006), and CTs (p = 0.02), and lower serum levels of SH-groups (p = 0.03) and ceruloplasmin (p = 0.03) compared with Group 2. The concentration of most studied indicators of pro- and antioxidant status did not depend on the severity of the acute phase COVID-19, and only catalase activity was statistically significantly related to the need for hospitalization (r = 0.59;p = 0.001), oxygen support (r = 0.44;p = 0.02), and the percentage of lung injury according to computed tomography (p = 0.03). Although the serum concentration of transferrin did not differ between the studied groups, the individual analysis showed that its value was statistically higher in HD patients with severe COVID-19 even 3.5 months after infection (p < 0.0001). Conclusions. Long-term COVID-19 sequelae in HD patients are associated with oxidative stress. High levels of catalase activity and serum transferrin 3.5 months after COVID-19 may be a consequence of the severe course of the acute phase of the disease. The obtained data suggest that the use of antioxidants may be one of the possible strategies to treat the long-term consequences of COVID in HD patients. © N. Stepanova, L. Korol, L. Snisar, A. Rysyev, T. Ostapenko,V. Marchenko, O. Belousova, O. Popova, N. Malashevska, M. Kolesnyk, 2023. All rights reserved.
ABSTRACT
BACKGROUND: A multicenter, double-blind, placebo-controlled, randomized clinical trial (RCT) of the phase III efficacy and safety of Ergoferon® for the non-specific prevention of COVID-19 during vaccination against a new coronavirus infection was conducted (permission of the Ministry of Health of the Russian Federation â559 dated 22.09.2021; ClinicalTrials.gov Identifier: NCT05069649). AIM: To evaluate the efficacy and safety of the use of Ergoferon for the non-specific prevention of COVID-19 during vaccination against a new coronavirus infection. MATERIALS AND METHODS: From October 2021 to April 2022, 1,057 patients aged 18 to 92 years who received component I of the "Gam-COVID-Vac" vaccine were included. After screening, 1,050 patients were randomized into 2 groups: 526 people received Ergoferon according to the prophylactic scheme - 1 tablet per administration 2 times a day for 3 weeks, the drug is not allowed during the meal and should be kept in the mouth without swallowing, until completely dissolved; 524 patients received a placebo according to the Ergoferon® scheme. The total duration of participation in the study was 5 weeks + 3 days. The primary endpoint is the number of RT-PCR - confirmed cases of SARS-CoV-2 infection, regardless of the presence of symptoms during participation in the study. An additional criterion of effectiveness is the proportion of those hospitalized with COVID-19. The safety assessment included consideration of the presence and nature of adverse events (AEs), their severity, relationship with the drug intake, and outcome. Statistical data processing was carried out using SAS 9.4 with the calculation of the exact Fisher test, χ2 test, Cochrane-Mantel-Hensel test, Wilcoxon test and other parameters. RESULTS: The ITT (Intention-to-treat) and PP [Per Protocol] efficacy analysis included data from 1,050 [970] patients: 526 [489] people - Ergoferon® group and 524 [481] people - Placebo group. The primary endpoint - the number of laboratory-confirmed cases of SARS-CoV-2 infections was 3 times less compared to placebo - 7 (1.43%) vs 22 (4.57%), respectively (p=0.0046; [p=0.0041]). Taking Ergoferon® reduces the risk of SARS-CoV-2 infection by more than 3 times in vaccinated patients during 5 weeks of the vaccination and post-vaccination periods (p=0.0046 [p=0.0041]). Of the COVID-19 patients in the Ergoferon® group (1.33%) nobody was hospitalized. According to the Post hoc analysis, Ergoferon® reduces the risk of COVID-19 disease by 4 times in the period between the components I and II of the "Gam-COVID-Vac" vaccine (p=0.0066 [p=0.006]). The frequency of AEs in both groups did not differ. There were no registered AEs associated with the drug with a reliable degree. There was a high level of patient compliance and good tolerability. CONCLUSION: Ergoferon is an effective and safe drug for the prevention of COVID-19 in people vaccinated against a new coronavirus infection.