Vol 93, No 11 (2021)

Aim. To study the relationship of hemostatic disorders with inflammation and estimate their role in the course and outcomes of COVID-19.

Materials and methods. We examined 215 consecutive patients with moderate and severe forms of acute COVID-19. The patients were on anticoagulants and immunosuppressive drugs. Hemostasis was assessed using the thrombodynamics assay, thromboelastography, fibrinogen and D-dimer levels, prothrombin time, and soluble fibrin-monomer complexes (ethanol gelation test). The hemostatic parameters were correlated with hematological and biochemical tests, including markers of inflammation (C-reactive protein, interleukins 6 and 8), as well as with the disease severity and outcomes.

Results. Laboratory signs of coagulopathy were revealed in the vast majority of the cases. Despite the use of low-molecular-weight heparins in the prophylactic and therapeutic doses, coagulopathy in COVID-19 manifested predominantly as hypercoagulability that correlated directly with the systemic inflammation and metabolic changes due to liver and kidney dysfunction. A direct relationship was found between the grade of coagulopathy and the severity of COVID-19, including comorbidities and the mortality. The chronometric hypocoagulability observed in about 1/4 cases was associated with a high level of C-reactive protein, which may decelerate coagulation in vitro and thereby mask the true inflammatory thrombophilia. Persistent hyperfibrinogenemia and high D-dimer in the absence of consumption coagulopathy suggest the predominance of local and/or regional microthrombosis over disseminated intravascular coagulation.

Conclusion. The results obtained substantiate the need for laboratory monitoring of hemostasis and active prophylaxis and treatment of thrombotic complications in COVID-19.

Aim. To estimate graft function after kidney transplantation during active herpesviruses or superinfection

Materials and methods. The study included 32 patients (men – 21, women – 11) with end-stage chronic kidney disease. The median age was 43 years. Cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6) DNAs were screened by RT-PCR in the donor's transplant biopsy, and recipients’ peripheral blood and urine after kidney transplantation (KT) on 0, 1, 2, 4, 6, 12 months. Antiviral antibodies (IgM and IgG) were also screened by Enzyme-linked immunoassay analysis (ELISA) along with PCR. The 500 or less copies of viral DNA per 10⁵ nuclear cells or 1 ml of urine was considered as low, more than 1000 copies – high.

Results. On the first month after KT CMV DNA was detected in 50% of pts., EBV DNA – in 40% and HHV-6 DNA – in 33%. During first year after KT two or three viruses simultaneously were found in 12 recipients: CMV, EBV, and HHV-6 were detected in 5 recipients; CMV and EBV – in 4 patients; CMV and HHV-6 – in 2 pts; EBV and HHV-6 – in 1 pt. Graft dysfunction was observed in 9 patients with a high concentration of viral DNA of one, two or three viruses simultaneously. An upraise of the concentration of virus DNA (CMV, EBV and HHV – 6) was detected primarily in the urine, while in the blood its concentration was less than 500 cop or undetectable. Renal dysfunction was not observed on the background of low concentrations of viral DNA in urine and blood. However, with an increase of DNA concentration, an impaired graft function in 8 of 12 patients appeared. Low viral DNA level proved to be a background for another virus activation or bacterial/fungal superinfection.

Conclusion. Graft dysfunction occurs at high viral DNA levels detection during mono-or superinfection. Low viral load can serve as a background for another virus activation and/or bacterial/fungal superinfection.

Background. The search for an aetiology of central nervous system (CNS) lesions In HIV patients can be extremely challenging.

Aim. To establish the nature and character of CNS lesion according to the data of pathological examination of deceased HIV-patients who had an antemortem clinical diagnosis of unspecified encephalitis.

Materials and methods. We analysed clinical and laboratory data of 225 HIV-patients admitted to the ICU at the Infectious Clinical Hospital №2 (Moscow, 2018). The principal diagnosis was unspecified encephalitis characterized by cerebral oedema. Had died 183 (67.9%) patients. We conducted pathological examination in 43 (23.5%).

Results. CNS lesions occurred in 331 patients (58.8% of 563 ICU). The antemortem diagnosis established were as follows: 12.1% – toxoplasmosis; 6.6% – HIV-encephalitis; 5.1% – CNS lymphoma; 3.6% – cryptococcal meningoencephalitis; 3.0% – cytomegaloviral diseases; 2.1% – progressive multifocal leukoencephalopathy. The cause of the pathology remained unidentified in 225 patients (68% with CNS lesions). Majority of patients were ART-naive. Post-mortem verification was conducted in 29 (67.4%) deceased patients, of which HIV-encephalitis – 34.5%, toxoplasmosis – 10.3%, progressive multifocal leukoencephalopathy – 3.4%. The nature of brain damage in the remaining 20.7% cases was not established even after post-mortem investigation. Productive lepto-meningitis – 8 (27.6%), indicating a prolonged duration of the inflammatory process. In the brain 48.1% patients with subacute and productive changes, had a pre-hospital time of more than 30 days, in contrast to 11.1% of patients who had acute pathological processes in the CNS (p<0.05). Autopsy didn’t reveal any inflammatory changes in the brain in 14 (32.6%) patients, though cerebral oedema – 93.3%, haemorrhagic syndrome – 60% cases.

Conclusion. Accurate retrospective identification of the aetiology of CNS lesions combined with assessing in vivo characterisation of the pathological process plays an essential role in subsequent formation of diagnostic approaches in pathologies of the CNS in HIV-patients.

Aim. To study the efficacy and safety of bulevirtide, the HBV and HDV entry inhibitor.

Materials and methods. Analysis of the results of using bulevirtide in randomized controlled open-label comparative studies MYR202 and MYR203 in 56 patients with chronic hepatitis D and compensated cirrhosis, in monotherapy and combination with pegylated interferon alpha-2a (PEG-IFN).

Results. Monotherapy with bulevirtide for 24 weeks in the MYR202 study in 46 patients with compensated liver cirrhosis demonstrated: 1) a high rate of virological (100%) and biochemical response (alanine aminotransferase normalization rate – 45.7%), 2) superiority of bulevirtide in efficacy over the control group (tenofovir), 3) comparability of treatment efficacy in patients with and without cirrhosis, 4) no progression of liver fibrosis with elastometry in most patients.

Treatment with bulevirtide in monotherapy and combination with PEG-IFN for 48 weeks in 10 patients with compensated liver cirrhosis in the MYR203 study was accompanied by a high rate of virological response (80%) and normalization of alanine aminotransferase (70%).

Bulevirtide was well tolerated, there was no deterioration in tolerability compared with patients without cirrhosis, there were no serious adverse events and cases of treatment cancellation due to adverse events.

Conclusion. Bulevirtide is recommended as the first line of treatment for chronic hepatitis D in patients with compensated cirrhosis in monotherapy and combination with PEG-IFN.

Aim. An analysis of coronavirus infection in Russia and evaluation of different AVT regimens effectiveness.

Materials and methods. The study involved a retrospective analysis of 1082 patient records with laboratory-confirmed COVID-19 in 17 regions of Russia. The number of men and women was equal, mean age – 48.7±18.1 (median – 50). Patients with moderate COVID-19 (85%) versus mild COVID-19 (15%) were characterized by higher age (median – 54 vs 21 years; p<0.001), higher body mass index (27.8 vs 23.4; p<0.001), prevalence of chronic diseases (75.3% vs 8.5%; p<0.001), including circulatory system diseases (37.8%). Moderate COVID-19 characterized higher intoxication (10.8±6.1 vs 4.2±2.7 days; p<0.001) and catarrhal symptoms duration (10.2±5.4 vs 6.1±4.1 days; p<0.001).

Results. During hospitalization 92% of the patients received AVT, 77% – antibiotics, and 16% – corticosteroids. Umifenovir therapy resulted in a significant reduction of intoxication (8.7±5.5 vs 11.7±5.5 days; p<0.001) and catarrhal symptoms duration (8.8±5.1 vs 12.0±4.9 days; p<0.001) compared to the group without AVT. The usage of INF reduced intoxication symptoms compared with the group without AVT (8.9±7.5 vs 11.7±5.5; p<0.05). Therapy with hydroxychloroquine, imidazolylethanamide pentandioic acid, and lopinavir + ritonavir combination did not affect the course of COVID-19. Most of adverse reactions were related to antibiotics.

Conclusion. Umifenovir therapy and inclusion of interferon in AVT regimens was associated improvement in the clinical manifestation of the disease among patients.

Background. Present concepts of the novel coronavirus infection prognosis in haemodialysis (HD) patients are rather controversial. There is little information on therapy efficiency and safety in such patients. We studied COVID-19 course specifics, prognostic factors associated with fatal outcomes, therapy efficiency and its transformation at different stages of the pandemic first year.

Materials and methods. Single-centre retrospective uncontrolled study included 653 COVID-19 HD-patients treated at Moscow City Nephrology Centre from April 1 to December 31, 2020.

Results. This period mortality rate was 21.0%. Independent predictors of COVID-19 unfavourable outcome in HD patients were pulmonary lesion extension (CT grades 3–4), high comorbidity index, and mechanical ventilation. Approaches to COVID-19 treatment modified significantly at different periods. Immunomodulatory drugs (monoclonal antibodies to IL-6, corticosteroids) were used largely at later stages. With tocilizumab administration, mortality was 15.1%, tocilizumab together with dexamethasone – 13.3%; without them – 37.8% (р<0,001). Tocilizumab administration in the first 3 days after hospitalization of patients with CT grades 1–2 was associated with more favourable outcomes: 1 out of 29 died vs 6 out of 20 (tocilizumab administered at later periods); p<0.04. There was no significant difference in death frequency in patients with CT grades 3–4 depending on tocilizumab administration time.

Conclusion. COVID-19 in HD patients can manifest in a severe course with unfavourable outcome. It is urgent to identify reliable disease outcome predictors and develop efficient treatment in this population.

Aim. To establish the equivalent efficacy and comparable safety profile of biosimilar Acveris and referent eculizumab product Soliris used for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

Materials and methods. Were included in the phase III multicenter 28 PNH patients, open-label clinical trial. Participants were randomized (1:1) into 2 treatment groups: investigational product (Acveris, n=14) and referent product (Soliris, n=14). Patients received eculizumab as the intravenous infusion 600 mg once a week during the first 4 weeks, 900 mg at week 5 and then 900 mg every 14 days (±2 days) up to week 27 of the study. The efficacy, pharmacokinetics, pharmacodynamics, safety and immunogenicity of the compared products were analyzed after the end of 27 weeks of the study. The primary efficacy endpoint was the area under the curve “LDH concentration–time” (AUC_LDH) throughout the study period weeks 5–27.

Results. The difference between the mean AUC_LDH values between the Acveris and Soliris groups was 5380.0 [-38 773.87; 49 533.87] U/l×days. The 95% CI limits for the difference in mean AUC_LDH values between the groups fit the preset 95% CI [-146 500.9–146 500.9] U/l×days and establish the equivalent efficacy of the biosimilar and referent product according to the primary efficacy endpoint. The safety profile of both Acveris and Soliris was expected and comparable according to the proportion of patients with adverse events. The formation of binding antibodies to eculizumab was not detected in both the groups.

Conclusion. The study established the equivalent efficacy of biosimilar product Acveris and referent eculizumab product with the evidence of effective suppression of intravascular hemolysis in PNH patients along with a comparable favorable safety profile.

The article considers a case from clinical practice: a mixed infection of viral hepatitis A and hemorrhagic fever with renal syndrome. Hepatitis had a protracted course and proceeded with the development of acute hepatic encephalopathy. Hemorrhagic fever was characterized by an atypical course with lung and heart damage.

The article describes a clinical observation of a severe course of a sporadic case of foodborne botulism in a woman at 32 weeks gestation with a successful resolution of pregnancy by independent childbirth. No adverse effects of botulism on pregnancy, delivery, and fetal development were noted. Anti-botulinum serum was administered to the patient no earlier than 96 hours from the onset of the disease. The paper analyzes the clinical picture of botulism, on the basis of which it is necessary to carry out a differential diagnosis.

While accidentally detecting an adrenal gland lesion (incidentaloma) during a routine computed tomography (CT) scan, the radiologist should correctly interpret revealed changes. The most common lesion is adenoma with high lipid content, but a lipid poor adenoma, pheochromocytoma, adrenocortical cancer, metastasis and other less common adrenal diseases are also worth of attention and require detailed knowledge of their CT semiotics. The article presents criteria of differential diagnosis of the adrenal incidentalomas on the basis of which an algorithm of differential diagnosis was proposed for the most common adrenal lesions.

In December 2019, in Wuhan (PRC), there was an outbreak of a new coronavirus infection (COVID-19) caused by coronavirus type 2 (SARS-CoV-2), which has a zoonotic origin. The World Health Organization announced the COVID-19 pandemic on March 11, 2020. In most cases, the disease is asymptomatic or mild. However, up to 15% of patients require hospitalization, and 5% develop a critical condition. To date, no effective antiviral drug COVID-19 has been found that can reduce mortality. Pathological changes in the lungs are manifested by diffuse alveolar damage, which is clinically manifested by increasing respiratory failure, accompanied by a decrease in saturation and oxygen concentration in arterial blood. It is assumed that autoimmune reactions play an important role in the development of multiple organ failure. Generalized inflammation is characterized by an increase in the concentration of C-reactive protein, ferritin, interleukin-1 and interleukin-6, and other markers. At the stage of development of infection in the form of a cytokine storm, proinflammatory cytokines can themselves become pathogenetic factors in the development of critical conditions, multiple organ failure and deaths. Therefore, a key challenge in treating hospitalized patients with COVID-19 is to control generalized inflammation. Glucocorticosteroid hormones (GCS) are widely used as anti-inflammatory drugs in the clinic of infectious diseases. However, until recently, there was no convincing data on the effectiveness of GCS in patients with COVID-19. Recently published results of a large randomized clinical trial (RECOVERY) showing the efficacy of GCS (dexamethasone) in the treatment of critically ill patients with COVID-19. At the same time, the feasibility and effectiveness of GCS in patients with COVID-19 outside critical conditions, the pathogenetic mechanisms that determine the effectiveness/ineffectiveness of these drugs and the validity of their use remain insufficiently studied.

The review provides a brief historical outline of the discovery and study of tick-borne encephalitis (TBE) during three expeditions to the Far East (1937–1939). As a result of the Far Eastern expeditions, the TBE virus was discovered, numerous strains were isolated, a vector-borne transmission pathway was established, the main features of epidemiology, clinic and pathomorphology of the disease were described, serotherapy was tested, first inactivated "brain" vaccine against TBE was developed and its effectiveness was proved. The history of the discovery and study of TBE is marked by the heroism of researchers and tragic events – illness of some participants, death during the development of the first vaccine, arrest of L.A. Zilber and two performers.