The Role of Genetic Factors in the Development of Acute Respiratory Viral Infection COVID-19: Predicting Severe Course and Outcomes.

The aim of this study was to identify single nucleotide variants in genes associated with susceptibility to or severe outcomes of COVID-19. A total of 319 genomic DNA samples from patients with varying degrees of disease severity and 78 control DNA samples from people who had regular or prolonged contact with patients with COVID-19 but did not have clinical manifestations and/or antibodies to SARS-CoV-2. Seven SNPs were identified that were statistically associated with disease risk or severe course, rs1799864 in the CCR2 gene (OR = 2.21), rs1990760 in the IFIH1 gene (OR = 2.41), rs1800629 in the TNF gene (OR = 1.98), rs75603675 in the TMPRSS2 gene (OR = 1.86), rs7842 in the C3AR1 gene (OR = 2.08), rs179008 in the gene TLR7 (OR = 1.85), rs324011 in the C3AR1 gene (OR = 2.08), rs179008 in the TLR7 gene (OR = 1.85), and rs324011 in the STAT6 gene (OR = 1.84), as well as two variants associated with protection from COVID-19, rs744166 in the STAT3 gene (OR = 0.36) and rs1898830 in the TLR2 gene (OR = 0.47). The genotype in the region of these markers can be the criterion of the therapeutic approach for patients with COVID-19.

Novel prognostic determinants of COVID-19-related mortality: A pilot study on severely-ill patients in Russia.

COVID-19 pandemic has posed a severe healthcare challenge calling for an integrated approach in determining the clues for early non-invasive diagnostics of the potentially severe cases and efficient patient stratification. Here we analyze the clinical, laboratory and CT scan characteristics associated with high risk of COVID-19-related death outcome in the cohort of severely-ill patients in Russia. The data obtained reveal that elevated dead lymphocyte counts, decreased early apoptotic lymphocytes, decreased CD14+/HLA-Dr+ monocytes, increased expression of JNK in PBMCs, elevated IL-17 and decreased PAI-1 serum levels are associated with a high risk of COVID-19-related mortality thus suggesting them to be new prognostic factors. This set of determinants could be used as early predictors of potentially severe course of COVID-19 for trials of prevention or timely treatment.

Tracheostomy management in patients with severe acute respiratory distress syndrome receiving extracorporeal membrane oxygenation: an International Multicenter Retrospective Study.

BACKGROUND: Current practices regarding tracheostomy in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown. Our objectives were to assess the prevalence and the association between the timing of tracheostomy (during or after ECMO weaning) and related complications, sedative, and analgesic use. METHODS: International, multicenter, retrospective study in four large volume ECMO centers during a 9-year period. RESULTS: Of the 1,168 patients treated with ECMO for severe ARDS (age 48 ± 16 years, 76% male, SAPS II score 51 ± 18) during the enrollment period, 353 (30%) and 177 (15%) underwent tracheostomy placement during or after ECMO, respectively. Severe complications were uncommon in both groups. Local bleeding within 24 h of tracheostomy was four times more frequent during ECMO (25 vs 7% after ECMO, p < 0.01). Cumulative sedative consumption decreased more rapidly after the procedure with sedative doses almost negligible 48-72 h later, when tracheostomy was performed after ECMO decannulation (p < 0.01). A significantly increased level of consciousness was observed within 72 h after tracheostomy in the "after ECMO" group, whereas it was unchanged in the "during-ECMO" group. CONCLUSION: In contrast to patients undergoing tracheostomy after ECMO decannulation, tracheostomy during ECMO was neither associated with a decrease in sedation and analgesia levels nor with an increase in the level of consciousness. This finding together with a higher risk of local bleeding in the days following the procedure reinforces the need for a case-by-case discussion on the balance between risks and benefits of tracheotomy when performed during ECMO.

Optically transparent electrodes to study living cells: A mini review.

The use of electrochemical methods to study living systems, including cells, has been of interest to researchers for a long time. Thus, controlling the polarization of the electrode contacting living cells, one can influence, for example, their proliferation or the synthesis of specific proteins. Moreover, the electrochemical approach formed the basis of the biocompatibility improvement of the materials contacting with body tissues that use in carbon hemosorbents and implants development. It became possible to reach a fundamentally new level in the study of cell activity with the introduction of optically transparent electrodes in this area. The advantage of the using of optically transparent electrodes is the possibility of simultaneous analysis of living cells by electrochemical and microscopic methods. The use of such materials allowed approaching to the study of the influence of the electrode potential on adhesion activity and morphology of the different cell types (HeLa cells, endothelial cell, etc.) more detailed. There are a negligible number of publications in this area despite the advantages of the usage of optically transparent electrodes to study living cells. This mini-review is devoted to some aspects of the interaction of living cells with conductive materials and current advances in the use of optically transparent electrodes for the study of living cells, as well as the prospects for their use in cellular technologies.

Impact of pathogen reduction methods on immunological properties of the COVID-19 convalescent plasma.

BACKGROUND AND OBJECTIVES: COVID-19 convalescent plasma is an experimental treatment against SARS-CoV-2. The aim of this study is to assess the impact of different pathogen reduction methods on the levels and virus neutralizing activity of the specific antibodies against SARS-CoV2 in convalescent plasma. MATERIALS AND METHODS: A total of 140 plasma doses collected by plasmapheresis from COVID-19 convalescent donors were subjected to pathogen reduction by three methods: methylene blue (M)/visible light, riboflavin (R)/UVB and amotosalen (A)/UVA. To conduct a paired comparison, individual plasma doses were divided into 2 samples that were subjected to one of these methods. The titres of SARS-CoV2 neutralizing antibodies (NtAbs) and levels of specific immunoglobulins to RBD, S- and N-proteins of SARS-CoV-2 were measured before and after pathogen reduction. RESULTS: The methods reduced NtAbs titres differently: among units with the initial titre 80 or above, 81% of units remained unchanged and 19% decreased by one step after methylene blue; 60% were unchanged and 40% decreased by one step after amotosalen; after riboflavin 43% were unchanged and 50% (7%, respectively) had a one-step (two-step, respectively) decrease. Paired two-sample comparisons (M vs. A, M vs. R and A vs. R) revealed that the largest statistically significant decrease in quantity and activity of the specific antibodies resulted from the riboflavin treatment. CONCLUSION: Pathogen reduction with methylene blue or with amotosalen provides the greater likelihood of preserving the immunological properties of the COVID-19 convalescent plasma compared to riboflavin.

Diagnosis and treatment of persons with acute thallium poisoning.

OBJECTIVE: This study aimed to describe organs and systems damages in persons after mass poisoning with thallium and show the results of treatment. METHODS: Forty-four persons (12 males and 32 females) with acute oral thallium poisoning were tested for thallium levels in blood and urine and examined by a toxicologist and a neurologist, and in some -cases, by a gynecologist, an ophthalmologist, and a psychiatrist. Persons were divided into the following three groups depending on the severity of the poisoning: I: This group consisted of 9 persons (blood thallium level 8.3-26.7 µg/L) and treatment applied in the hospital included intestinal lavage, antidote therapy with potassium-ferric hexacyanoferrate, sodium dimercaptopropanesulfonate; II: This group consisted of 21 persons (0.3-6.1 µg/L) who received a similar treatment at home; and III: This group consisted of 14 (normal) persons who did not receive any treatment. RESULTS: The most common combination of several symptoms such as alopecia (on day 17-23), muscle pain of different localization in the debut of the disease (>88.9 % of the persons), sudden unexplained general weakness (>76.2 % of the persons), peripheral paraparesis or tetraparesis (including no complaints), polyneuropathy (88.89 % in group I vs. 54.14 % in group II, p < 0.05), static and dynamic ataxia (33.3 % in group I vs. 19.4 % in group II, p < 0.05), vertigo (1/3 of the persons), postural tremor (1/3 of the persons), and cognitive and emotional disorders (2/3 of the persons). Ovarian dysfunction was observed in all women of group I but in 42.9 % of group II, p < 0.05. The treatment was successful. In group I, plasma and urine thallium level significantly decreased by 69.3 % and 84 %, respectively. Pain, movement and coordination disorders regressed first while tremor, sensory, cognitive and emotional disorders lasted longer. Polyneuropathies later became mononeuropathies. Tremor could increase despite a decreased thallium concentration. DISCUSSION: The Sklifosovsky Institute conducted the largest study in Russian Federation investigating disorders in persons with acute thallium poisoning confirmed by laboratory tests. The clinical symptoms were consistent with those reported in the literature. The applied treatment was successful and led to better results compared to our previous approaches of treating mass thallium poisoning. CONCLUSIONS: This study shows a typical combination of thallium poisoning symptoms and allows us to recommend a complex therapy without the use of extracorporeal detoxification methods.

Thermovaccination - thermoheliox as a stimulator of the immune response. Kinetics of the synthesis of antibodies and C-reactive protein in coronavirus infection.

Clinical trials of thermoheliox application (inhalation with a high-temperature mixture of oxygen and helium, 90 °C) in the treatment of the acute phase of coronavirus infection were conducted. Dynamics of disease development in infected patients (PCR test for the virus) and, dynamics of changes in blood concentration of C-reactive protein, immunoglobulin M, specific immunoglobulin G were studied. High efficiency of thermoheliox in releasing the organism from the virus and stimulating the immune response (thermovaccination effect) was shown. The kinetic model of the process is proposed and analyzed.

Clinical and pathophysiologic aspects of ECMO-associated hemorrhagic complications.

Extracorporeal membrane oxygenation (ECMO) is increasingly used to treat severe cases of acute respiratory or cardiac failure. Hemorrhagic complications represent one of the most common complications during ECMO, and can be life threatening. The purpose of this study was to elucidate pathophysiological mechanisms of ECMO-associated hemorrhagic complications and their impact on standard and viscoelastic coagulation tests. The study cohort included 27 patients treated with VV-ECMO or VA-ECMO. Hemostasis was evaluated using standard coagulation tests and viscoelastic parameters investigated with rotational thromboelastometry. Anticoagulation and hemorrhagic complications were analyzed for up to seven days depending on ECMO duration. Hemorrhagic complications developed in 16 (59%) patients. There were 102 discrete hemorrhagic episodes among 116 24-hour-intervals, of which 27% were considered to be clinically significant. The highest number of ECMO-associated hemorrhages occurred on the 2nd and 3rd day of treatment. Respiratory tract bleeding was the most common hemorrhagic complication, occurring in 62% of the 24-hour intervals. All 24-hours-intervals were divided into two groups: "with bleeding" and "without bleeding". The probability of hemorrhage was significantly associated with abnormalities of four parameters: increased international normalized ratio (INR, sensitivity 71%, specificity 94%), increased prothrombin time (PT, sensitivity 90%, specificity 72%), decreased intrinsic pathway maximal clot firmness (MCFin, sensitivity 76%, specificity 89%), and increased extrinsic pathway clot formation time (CFTex, sensitivity 77%, specificity 87%). In conclusions, early ECMO-associated hemorrhagic complications are related to one traditional and two novel viscoelastic coagulation abnormalities: PT/INR elevation, reduced maximum clot firmness due to intrinsic pathway dysfunction (MCFin), and prolonged clot formation time due to extrinsic pathway dysfunction (CFTex). When managing hemostasis during ECMO, derangements in PT/INR, MCFin and CFTex should be focused on.