COVID-19 infection in hematopoietic stem cell transplant recipients.

Objective. To assess the course and outcomes of COVID-19 in recipients of allogeneic and autologous hematopoietic stem cell transplant (HSCT). Materials and methods. The retrospective study included 44 adult recipients (allogeneic - 33 [75%] and autologous - 11 [25%] of HSCT who diagnosed with COVID-19 after transplantation. Group mostly represented by acute leukemia - 18 (41%) and lymphoma - 10 (22.7%). The median follow-up time since the development of COVID-19 was 231 days (1-818 days), after HSCT - 507.5 days (14-3723 days). Overall and progression-free survival was assessed using the Kaplan-Meier and Log-Rank method. We also evaluated the characteristics of the course of a new coronavirus infection. Results. Median time for the development of COVID-19 from the moment of HSCT was 122.5 days (-1-3490 days). Twelve patients (27.2%) were in grade 3-4 neutropenia at the time of COVID-19 diagnosis, 16 (36.4%) patients were in grade 1-2 neutropenia. Sixteen (48.4%) allo-HSCT recipients had active graft-versus-host disease (GVHD) at the time of COVID-19 development. Disease severity was mild in 19 (43.2%) and moderate in 13 (29.5%) patients. Overall, 200-day survival from the onset of COVID-19 was 78.8% (95% CI [63.1-88.4]). Anemia (p = 0.02) and thrombocytopenia (p = 0.01) significantly decrease OS in patients with COVID-19 after HSCT. Patients with GVHD at the time of COVID-19 onset had a better survival rate (p = 0.02). The timing of COVID-19 development after HSCT did not affect outcomes. Conclusions. The key points of the course of COVID-19 in HSCT recipients are the presence of cytopenia and graft-versus-host disease. Overall survival was 78.8%.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Inflammation and endothelial toxicity: pathogenetic aspects of central nervous system damage due to novel coronavirus disease

Introduction. There are inconsistent data on the incidence of stroke in patients with COVID-19, including acute cerebrovascular accidents in younger people without obligate risk factors, as well as the riskof SARS-CoV-2infection in patients withacute stroke. The aimof the study was to evaluate the features of concomitant stroke andCOVID-19, andthe role of inflammation andendothelial toxicity in cerebral damage. Materials andmethods. The study included1,524patients admittedtovascular clinics across St. Petersburg in2020–2021, including 1,068people withconfirmed COVID-19infection and551deathcases. The patients were dividedinto four groups depending on disease severity, for clinical andlaboratory data analysis. Results. There were markedchanges in the laboratory markers of inflammation, haemostasis, fibrinolysis, cytolysis, iron metabolism, cerebral ischaemia, proteolysis, immunodeficiency (lymphocytopenia, monocytopenia, elevated white blood cell count, elevated levels of C-reactive protein, fibrinogen, D-dimer, creatine kinase, ferritinandneutrophilelastase), withstatistically significant differences whencomparedwithpatients without COVID-19. Changes ininflammatory markers in the first 24–72hours providedthe most information. Amultifoldincrease (escalation)in the marker values was always correlatedwithan imminent adverse outcome andwas usually accompaniedby subsequent laboratory confirmation of COVID-19infection or specific signs of viral pneumonia. Conclusion. COVID-19 should be considered an independent risk factor for acute stroke, while the virus-induced thrombosis, manifesting in an escalation in inflammatory factors and products of endothelial damage, shouldbe considereda pathogenetic linkleading to cerebral tissue damage. © 2022 Authors. All rights reserved.

Interleukin 6 receptor inhibitors in the treatment of rheumatoid arthritis during the COVID-19 pandemic, Moscow experience

Objective: to confirm the efficacy and safety of levilimab in patients with rheumatoid arthritis (RA) switched from other interleukin 6 receptor in-hibitors (iIL6R) for non-medical reasons. Patients and methods. A retrospective analysis of data from the register of patients with RA who during the COVID-19 pandemic were switched from foreign iIL6Rs to the Russian drug levilimab. Treatment regimens with levilimab in combination with synthetic disease-modifying antirheumatic drugs (sDMARDs) and/or glucocorticoids (GCs) were used, as well as a monotherapy regimen in case of DMARDs intolerance. Results and discussion. In 150 patients with RA, a successful non-medical switch to levilimab was demonstrated with the preservation and inten-sification of the clinical effect achieved on previous therapy with iIL6R. After switching to levilimab, the DAS28-CRP index decreased by an av-erage of 0.098 at 3 months and by 0.25 at 6 months (p=0.214 for both time points). There was a decrease in the proportion of patients with elevated levels of CRP, as well as with high RA activity. In a number of patients who showed high efficacy of levilimab, it became possible to reduce the dose or number of DMARDs, as well as cease GCs intake. Good tolerability and a favorable safety profile of levilimab were noted, including in relation to the new coronavirus infection that developed during therapy. Conclusion. Therapy with Russian iIL6R levilimab is effective and safe, including in patients switched from other drugs for non-medical reasons, as well as in relation to the novel coronavirus infection that developed during therapy. © 2022, Ima-Press Publishing House. All rights reserved.

COVID-19 in rheumatoid arthritis patients receiving baricitinib: Observations from patient registry

Background/Purpose: Rheumatoid arthritis (RA) patients have higher COVID-19 risks [1,2]. Data suggest that some RA biologics, including baricitinib, may be beneficial for COVID-19 outcomes [3,4]. We used data from RA registry to evaluate impact of COVID-19 on RA activity in patients receiving baricitinib. Method(s): Current study is a single center registry of RA patients receiving baricitinib as a part of routine treatment. Study center accumulates most of RA patients who started baricitinib in Moscow (Russia) from July 2020 to data cutoff (January 2022). We analyzed medical records data for demographics, disease history, and change of disease activity indexes. Medical record data were allocated to visit 1 (baseline), closest to 4 and 8 months after baricitinib initiation (visits 2 and 3). Patients, who had no baricitinib interruptions, were divided in strata according to COVID status between visits 1 and 2. Result(s): At the time of data cutoff registry included data from 142 RA patients receiving baricitinib. Median duration of treatment was 14.5 (interquartile range [IQR] 10-29) weeks. Clinical RA indexes measures are compiled in Table 1. Of 142 patients, 52 had COVID-19 between visits 1 and 2 without baricitinib interruption. Swollen joint counts (SJCs) and tender joint counts (TJCs) were comparable across 3 visits except TJC at visit 3 (P < 0.05). Disease Activity Score-28 for Rheumatoid Arthritis with C-Reactive Protein (DAS28-CRP), Disease Activity Score-28 for Rheumatoid Arthritis with Erythrocyte Sedimentation Rate (DAS28-ESR) had comparable change regardless of COVID-19 status (P > 0.05). Simplified Disease Activity Index for Rheumatoid Arthritis (SDAI) and Clinical Disease Activity Index (CDAI) were higher in COVID-19 survivors at visit 3 (P < 0.05). (Table Presented) Conclusion(s): We conclude that, overall, COVID-19 had no significant impact on RA activity during baricitinib treatment. Further follow-up needed to find out reasons for TJC/SDAI/CDAI increase in COVID-19 survivors >=4 months after infection.

COVID-19 infection in hematopoietic stem cell transplant recipients

Objective. To assess the course and outcomes of COVID-19 in recipients of allogeneic and autologous hematopoietic stem cell transplant (HSCT). Materials and methods. The retrospective study included 44 adult recipients (allogeneic – 33 [75%] and autologous – 11 [25%] of HSCT who diagnosed with COVID-19 after transplantation. Group mostly represented by acute leukemia – 18 (41%) and lymphoma – 10 (22.7%). The median follow-up time since the development of COVID-19 was 231 days (1–818 days), after HSCT – 507.5 days (14–3723 days). Overall and progression-free survival was assessed using the Kaplan–Meier and Log-Rank method. We also evaluated the characteristics of the course of a new coronavirus infection. Results. Median time for the development of COVID-19 from the moment of HSCT was 122.5 days (-1–3490 days). Twelve patients (27.2%) were in grade 3–4 neutropenia at the time of COVID-19 diagnosis, 16 (36.4%) patients were in grade 1–2 neutropenia. Sixteen (48.4%) allo-HSCT recipients had active graft-versus-host disease (GVHD) at the time of COVID-19 development. Disease severity was mild in 19 (43.2%) and moderate in 13 (29.5%) patients. Overall, 200-day survival from the onset of COVID-19 was 78.8% (95% CI [63.1–88.4]). Anemia (p = 0.02) and thrombocytopenia (p = 0.01) significantly decrease OS in patients with COVID-19 after HSCT. Patients with GVHD at the time of COVID-19 onset had a better survival rate (p = 0.02). The timing of COVID-19 development after HSCT did not affect outcomes. Conclusions. The key points of the course of COVID-19 in HSCT recipients are the presence of cytopenia and graft-versus-host disease. Overall survival was 78.8%. © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Excess Mortality in the Siberian Regions in the Context of the COVID-19 Pandemic: Dynamics and Affecting Factors

Introduction. The COVID-19 pandemic has had a strong negative impact on demographic processes in Russian regions. Mortality has increased significantly, the life expectancy has declined, and the natural decline in the population over the two pandemic years has reached ultra-high indicators. The article aims to analyze the dynamics of the mortality growth in the regions of Siberia for 2020-2021 and assess the impact of demographic, socio-economic, medical and infrastructure factors on it. Materials and Methods. The study is based on official statistical data for individual constituent entities of Russia published by Rosstat (Russian Statistics Agency). The regression and correlation analysis was used to identify the most significant factors that determined the increase and interregional differences in mortality displacement rates. Results. For the Siberian regions the significant factors that determine the increase and interregional differences in mortality displacement include the median age of the population;proportion of children in the age distribution structure;population of the regional capital;as well as the share of extractive and manufacturing industries in regional employment pattern. The median age of 39 and above, the low proportion of minors, and the specialization of a particular region in the manufacturing industry (implying more intensive contacts of employees) contribute to a significant increase in mortality during the pandemic. Regions of Siberia with a relatively low rate of mortality displacement have a younger age distribution structure and economic specialization in the extraction of minerals (contacts of the labor force are rather less frequent). The factors of urbanization level, average per capita income of the population, poverty incidence, general unemployment rate, number of hospital beds, and the number of doctors do not show a significant relationship with the increase in mortality. Discussion and Conclusion. The analysis established the causes of a significant increase in mortality in the Siberian regions. The leading role in it was played by demographic factors and economic specialization of the region. The results obtained can be used in the implementation of social and demographic policy aimed at maintaining the population health in regions with different demographic and socio-economic situations.

Journey of a hematopoietic stem cell transplantation center through COVID-19 pandemic: one-year experience

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for oncological, hematologi-cal and non-malignant disorders. Despite global trend for a decrease of transplantation activity in view of the COVID-19 pandemic, we tried to maintain it by taking preventive measures and optimizing infection control in our center. Patients and methods This is an observational study. We collected the performance data of our transplant center from April 2020 to July 2021, i.e., during two waves of the pandemic. The main objectives were to study the influence of COVID-19 pandemic on the workflow of the HSCT center, including morbidity among employees and HSCT recipients, as well as on the transplant activity. Results The first case of COVID-19 infection in St. Petersburg was recorded on March 8, 2020. On March 30, 2020, a national lockdown had been imposed in the Russian Federation. The second wave of COVID-19 started in October 2020. Weekly screening of staff and patients was the main diagnostic tool, in addition to the governmental requirements. In sum, a total of 21702 PCR tests for SARS-CoV-2 were performed over the study period. As for July 1, 2021, 69.7% of employees became immune to the virus, due to previous COVID-19 disease, or by vaccination. In 2020, we managed to perform 419 HSCT, including 136 autologous and 283 allogeneic transplants. For comparison, 415 HSCTs were carried out in 2019, with 144 autologous and 271 allogeneic transplants. In 2020, the HSC donorship was shifted towards unrelated donors from the Russian Registry and haploidentical donors. Incidence of COVID-19 among HSCT recipients between April 2020 and July 2021 was 7.3% (n=39), being 8.6% (n=31) after allogeneic HSCT, and 4.5% (n=8) following auto-HSCT. The median age of patients with COVID-19 was 27 years (4-66). The median term for the COVID-19 onset was 68 days post-transplant (-1 to +2093). In most patients – 29 (74.3%) the HCT CI comorbidity index at the time of transplantation was 0. The stem cell source were either peripheral blood stem cells (n=22, 56.4%), or bone marrow (n=17, 43.6%). Most of the patients achieved complete remission of the underlying disease at the time of HSCT (n=30, 76.9%). The overall 100-day survival rate among HSCT recipients since the diagnosis of the COVID-19 was 79.5% (95% CI 0.609 – 0.884). The mortality rate was 20.5% (n=8). The causes of death were as follows: COVID-19 – 50% (n=4);secondary infectious complications, 25% (n=2);relapse of the underlying disease, 12.5% (n=1);hemorrhagic complications, 12.5% (n=1). The 100-day cumulative incidence of transplant-related mortality (TRM) among all HSCT recipients was 7% (95% CI 0.9 – 0.95) and 8.7% (95% CI 0.88 – 0.93) in 2019 and 2020, respectively (p=0.35). Conclusions Due to preventive measures, regular PCR screening, as well as the use of donors from the Russian Registry or haploidentical donors, we managed to maintain HSCT activity at the same level. The COVID-19 morbidity of HSCT recipients was 7.3%, their mortality rate – 20.5%. In summary, the pandemic did not affect transplant-related mortality among the HSCT recipients in our center. © Universitatsklinikum Hamburg - Eppendorf. All rights reserved.

Robotic Glove Prototype: Development and Simulation

With the fast development in the field of the Internet of Things, remote control for laboratory equipment has the potential to grow up. Moreover, due to COVID-19 restrictions, it has rapid application in research and educational laboratories. This paper presents a robotic glove prototype based on sensors that can control the robotic fingers for remote operation of conventional laboratory test benches. The robotic glove prototype is implemented with an Arduino. An additional low pass filter is used to level down the remote measurement noise. The development approach used in a particular case study may be applied for remote control of similar devices. Designed mathematical models are publicly available on GitHub. © 2021 IEEE.

Gas transport characteristics of hemocorrectors and perfusates based on perfluorocarbon blood-substituting emulsions

This review summarizes the data regarding the gas transport characteristics of hemocorrection and perfusates on the basis of low concentrated drugs nano-sized perfluorocarbonic 20% Per-ftoran (a blood substitute, it is allowed for clinical use in Russia), 20% Ftoremulsion III (an improved blood substitute, registered in Russia), 10-20% Perfusol (a perfusion solution for perfusion of the isolated heart), 20% Ftorem (a cardioplegic emulsion for sur-geries on the stopped heart) used in the biomedical field. The com-pensation of blood loss using traditional plasma substitutes with-out the gas transport function or with low gas transport characteristics leads to a decrease in the oxygen capacity of the resulting mixture and subsequently to deterioration in the oxygen transport characteristics of blood. The synthetic gas-transport blood substitutes can be used in the treatment of various forms of ischemia, such as carbon monoxide poisoning. Furthermore, recent results regarding the mechanism of COVID19 infection indicate a possible use of the synthetic gas-transport blood substitutes in the treatment and therapy of COVID19 infected patients. © 2020, University of Kragujevac, Faculty of Science. All rights reserved.

Fundamental basis of covid-19 pathogenesis

At the end of 2019, a new coronavirus infection occurred in the People's Republic of China with an epicentre in the city of Wu-han. On February 11th, 2020, the World Health Organization as-signed the official name of the infection caused by the new coro-navirus – COVID-19. COVID-19 has affected people from all over the world given that the infection was noted in 200 countries resulting in annunciation of the pandemic situation. Human co-rona viruses cause mild to moderate respiratory infections. At the end of 2002, a new coronavirus appeared (SARS-CoV), the causal agent of atypical pneumonia, which caused acute respiratory distress syndrome (ARDS). The initial stage of COVID-19 infection is the penetration of SARS-CoV-2 into target cells that have angi-otensin converting enzyme type II receptors. The virus enters the body through the respiratory tract and interacts primarily with toll-like receptors (TLRs). The events in SARS-Cov-2 induced infection follow the next scenario: epithelial cells via TLRs recog-nize and identify SARS-Cov-2, and after that the information is transmitted to the transcriptional NF-κB, which causes expression of the corresponding genes. Activated in this way, the epithelial cells begin to synthesize various biologically active molecules. The results obtained on preclinical material indicate that ROS generation increases and the antioxidant protection decreases, which plays a major role in the pathogenesis of SARS-CoV, as well as in the progression and severity of this respiratory disease. © 2020, University of Kragujevac, Faculty of Science. All rights reserved.