Aim. To analyze the characteristics of novel coronavirus infection COVID-19 in hairy cell leukemia (HCL) patients and to assess humoral immune response in those of them who had COVID-19 and/or were vaccinated against SARS-CoV-2. Materials & Methods. This paper documents the retrospective analysis of the data from 118 HCL patients followed-up at the National Research Center for Hematology from March 2020 to October 2021. Within this period, 99 out of 118 patients had novel coronavirus infection COVID-19; 17 out of 99 COVID-19 patients were vaccinated against SARS-CoV-2 (3 of them prior to being infected and 14 of them after that). The rest of 19 HCL patients without COVID-19 were vaccinated against SARS-CoV-2 during the period from January to October 2021. By the time of HCL diagnosis, the patients were aged 23–74 years (median 47 years), whereas by the time of COVID-19 diagnosis, the age range was 25–82 years (median 55 years). There were 63 men and 36 women. Results. Severe CT 3–4 lung lesions were diagnosed in 22 (22 %) patients and detected more often (55 %) prior to therapy for advanced-stage HCL. In patients on therapy for advanced-stage HCL and those in remission, the rate of severe lung lesions (CT 3–4) was 17 % in each group. COVID-19 therapy was administered to 49 (49 %) patients in a special hospital. Mortality in the total cohort was 6 % (n = 6) and differed in patients with advanced-stage HCL (n = 4) and those in remission (n = 2). The patients who received anti-CD20 monoclonal antibodies for < 12 months prior to COVID-19 infection, in 42 % (n = 5) of cases showed seronegativity vs. 5 % (n = 1) of patients who received the same therapy > 12 months before COVID-19 was diagnosed. Conclusion. The most severe COVID-19 was observed in chemotherapy-free patients with advanced-stage HCL compared to patients on therapy or in HCL remission. When anti-CD20 monoclonal antibodies were administered for < 12 months prior to COVID-19 diagnosis, the number of patients with negative anti-SARS-CoV-2-IgG immune response increased 15-fold. Mortality in novel coronavirus infection COVID-19 differed at various HCL stages (in remission and at advanced stage).
Allogeneic hematopoietic stem cells transplantation is an effective method for the treatment of hematologic malignancies and other blood system diseases. Infections caused by human 6A and 6B herpes viruses are one of the leading causes of complications and mortality in hematology patients after allogeneic hematopoietic stem cell transplantation, especially in the first 100 days after transplantation. This review discusses the clinical features of infections caused by human herpes viruses 6A and 6B, their impact on the development of post-transplant complications, including graft-versus-host disease and graft failure, as well as methods of prevention and treatment.
The aim of the work is to improve the algorithm of management of pregnant women with HIV/HCV co-infection. The study was conducted on the basis of the Moscow City Center for AIDS Prevention and Control of the Moscow Department of Health from 2020 to 2022. 80 women diagnosed with HIV/HCV coinfection were under observation. The patients underwent a general examination and evaluation of anamnesis data, laboratory tests. The article presents statistical data on HIV/HCV-infected women who have been registered at the Moscow City Center for the Prevention and Control of AIDS for the past three years. The social characteristics of pregnant women with HIV/HCV co-infection are given and the clinical and immunological features of the course of the disease are presented.
Topic: 22. Stem cell transplantation - Clinical Background: A large number of reviews is devoted to affection of different types of graft-versus-host disease (GvHD) prophylaxis regimens on the reconstitution of the T-cell immunity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Association of the posttransplant cyclophosphamide (PT-CY) together with TCR αβ+/CD19+ cell depletion is associated with the deeper T cell deficiency after allo-HSCT. Cytomegalovirus (CMV) specific T lymphocytes transfusion as adoptive T cell therapy (ACT) can boost reconstitution of the CMV-specific immunity and provide long-term protection against CMV-infection. Aims: To evaluate the impact of ACT with using CMV-specific T cells on the reconstitution of CMV-specific T-cell immunity after allo-HSCT. Methods: Total 64 recipients of peripheral blood stem cells (PBSC) as the graft source after TCR αβ+/CD19+ cells depletion and PT-CY as GvHD prophylaxis were included in the analysis. Seventeen (26.5%) patients received ACT at the +30 day after the engraftment. All patients reached engraftment after allo-HSCT. Absolute count of CMV-specific T cells at +30, +90, +180 day after allo-HSCT in peripheral blood samples was estimated via flow cytometry analysis. The detection of CMV-specific T cells was performed by using tetramers formed from MHC class I monomers loaded with immunodominant epitopes of cytomegalovirus pp65 protein (HLA-A*02/NLV, HLA-B*07/TPR, HLA-B*07/RPH) and Streptavidin, R-Phycoerythrin conjugate (SAPE). We formed two groups due to the presence of the ACT after engraftment. These groups were balanced by two main factors affecting CMV-specific immunity: GvHD prophylaxis regimen and CMV-serologic status of Donor-Recipient pairs (D/ R). Results: As shown in figure 1 the absolute number of CMV-specific T cells had not significantly differed between groups before ACT (on day +30). After that on day +90 in the group with CMV-specific T cell transfusion the number of CMV-specific T cells was significantly higher compared to the group without ACT (p=0.013).Figure 1. The comparison of the absolute count of CMV-specific T cells (cell/µl) in peripheral blood samples at +30, +90, +180 day after allo-HSCT depending on the use of adoptive T cell therapy. Summary/Conclusion: Transfusion of donor CMV-specific T-lymphocytes after the engraftment from +30 day after allo-HSCT effectively boost the reconstruction of CMV-specific immunity in patients with highly aggressive GvHD prophylaxis regimens, including PT-CY and TCR αβ+/CD19+ cells depletion. Thus, tge presence of the ACT in prophylaxis protocols for management of CMV infection after allo-HSCT can accelerate virus‐specific immune reconstitution. Keywords: CMV infection, Adoptive immunotherapy, Stem cell transplant, T cell reconstitution
Introduction. Testing for antibodies to the causative agent COVID-19 is not mandatory for donor blood or its components. It is unknown whether transfusion of plasma-containing blood components from seropositive donors is a safe procedure especially for immunocompromised hematological patients. Aim. To assess the frequency of adverse reactions and complications in hematological patients after transfusions of plasma-derived blood products harvested from anti-SARS-CoV-2 positive and negative donors. Material and Methods. 9152 transfusions of components harvested from anti-SARS-CoV-2 positive and negative donors were carried out from April 29, 2020 to January 21, 2022 at the NMRC for Hematology. Post-transfusion reactions and complications were analyzed in 576 hematological patients. 2059 plasma units, 327 cryosupernatant plasma units and 6766 cryoprecipitate doses were assessed. The occurrence of adverse reactions (hyperthermia) and complications within two hours after transfusion were evaluated. Results. Among 9152 blood units, anti-SARS-CoV-2 were detected in 2660 (29 %) cases and 6492 (71 %) were antibodies free. The analysis of adverse reactions and complications showed no significant differences in the incidence of adverse reactions in recipients after anti-SARS-CoV-2 positive and negative blood unit transfusions. Conclusion. There were no significant differences in the number of post-transfusion reactions when using donor blood components (fresh frozen plasma, cryosupernatant plasma, cryoprecipitate) obtained from donors in whose blood antibodies to SARS-CoV-2 were detected or not detected. Plasma-derived blood products from seropositive donors with a high degree of probability can be used to correct the plasma hemostasis path in hematological patients along with components prepared from seronegative donors.
Introduction . Transfusions of donor blood components are indispensable in providing medical care for a large number of conditions and diseases. Therefore, the issue of improving the quality and safety of transfusions is relevant for healthcare worldwide. Aim — to assess the quality of donor blood screening for HIV, HBV and HCV by PCR in several Russian blood banks. Methods : PCR, CLIA and ELISA. Results. A study was conducted to assess the quality of molecular screening of donated blood in medical organizations, which was carried out in two stages. Two different kits of control samples for each project stage were created and delivered to the project participants (blood banks). Each kit contained samples with or without HBV DNA / HIV RNA / HCV RNA. The first stage’s kit contained 40 samples, the second one — 10 samples. Thus, project participants performed 13 series of test runs (520 tests) on the first stage and 8 series of runs (80 tests) on the second one. The number kits copies sent to one participant was determined by the participant’s laboratory equipment. Participants who used the Cobas performed 330 tests, of which 255 were incorrect. Participants using the Procleix performed 40 tests, and 29 tests gave a false result. 140 samples were tested by AmpliSens, and results in 86 cases were incorrect. One participant used Vector-Best test kits and performed 40 tests, 16 of which returned incorrect. In total, 355 samples containing HBV DNA, 121 samples containing HCV RNA, and 82 samples containing HIV RNA were provided to project participants. HBV DNA was detected in 191 (53.8 %) of 355 samples, HCV RNA was detected in 119 (98.3 %) of 121 samples, and HIV RNA was detected in 76 (92.7 %) of 82 samples. Conclusion . The proportion of inconsistencies in the results increased depending on the decrease in the concentration of the marker being determined. Participants demonstrated the best performance results if they were using branded equipment. Such participants received the least inconsistencies. The biggest issue concerned HBV DNA detection due to a lower viremia of this pathogen. All samples with low HBV DNA levels contained anti-HBc, which indicates potential latent HBV. Therefore, it is appropriate to include anti-HBc in the routine screening of donated blood.
Background. COVID-19 required fundamental changes in healthcare management, also in medical care for oncological and hematological patients. Visits to healthcare organizations were minimized, 75 % of doctor appointments were converted to telemedicine consultations. The solutions aimed at preventing further spread of COVID-19 included establishing of observational units, distinguishing between patient and employee flows, regular SARS-CoV-2 RNA testing, reducing hospital stays and transferring patients with positive COVID-19 tests to the remodeled hospitals specializing in the novel coronavirus infection, as well as providing only emergency medical treatment and, as far as feasible, converting systemic chemotherapy to per os treatment, etc. Aim. To assess SARS-CoV-2 RNA detection dynamics at the National Research Center for Hematology from April 2020 to January 2022 during the implementation of epidemic control measures. Materials & Methods. The study was based on SARS-CoV-2 RNA testing of naso- and oropharyngeal samples obtained from patients and employees of the National Research Center for Hematology (hereafter referred to as Center). Besides, bronchoalveolar lavage fluid, lung tissue biopsies, and sputum were examined for SARS-CoV-2 RNA. The study was performed at the Center’s Virusology Department with the use of Sintol reagent kit “ПЦР-РВ-2019-nCov”. Results. The study was based on 107,470 tests: 58,141 (54 %) of employees and 45,126 (46 %) of patients; 35,508 (33 %) of men and 71,962 (67 %) of women. In 1318 cases SARS-CoV-2 RNA was detected which accounted for 1.15 % of total test number. In the groups of employees/patients, virus detection rate was 1.42 %/1.09 % (p < 0.001), and in male/female groups it was 1.3 %/1.2 %, respectively (p = 0.154). The rate of infection in the groups of tumor and non-tumor hematological patients, as proved by SARS-CoV-2 RNA testing, was 1.24 % and 0.92 %, respectively (p = 0.147). In employees and patients of the Center, a wave-like virus detection rate was observed. The largest number of infections was registered in April-June 2020 (79 patients and 170 employees), October-December 2020 (126 patients and 190 employees), and January 2022 (59 patients and 203 employees), which corresponded to the first, second, and fifth COVID-19 waves in Russia. Conclusion. The analysis of data obtained at the National Research Center for Hematology demonstrated a wave-like SARS-CoV-2 RNA detection rate in employees and patients of the Center, which corresponded to the general trend in Russia. The SARS-CoV-2 RNA detection rate did not depend on sex of subjects under study and was not significantly different in the groups of tumor and non-tumor hematological patients. Although the patients in hematological hospital are more exposed to the risk of severe infectious complications, they showed laboratory markers for COVID-19 less frequently than the Center employees.
Introduction. Ensuring a sustainable supply of safe donor blood is crucial for strategic issues and challenges. The evaluation of donor characteristics as well as the volume of components harvested and issued to medical organizations in the Russian Federation is a topical task for the national blood service.Aim — to analyze the performance indicators of the national blood service for the procurement and provision of donated blood and its components to medical organizations from 2016–2020.Methods. Data on over 6.5 million donors who donated blood in Russia during 2016–2020 were analyzed. Data were obtained from Blood Service report form No. 39 “Blood products and derivatives”. Descriptive statistics were used during analysis.Results. A decrease of the number of blood donors per thousand population was shown (from 9.68 to 8.26, р < 0.0001). There was a decrease of the number of first-time donors and of the number of repeat donors (by 23 and 9.3 %, respectively) within studied period. Regular donor quantum increased from 71 to 76 %. The share of volunteer blood donors from 2016 to 2020 throughout the Russian Federation remained stable and amounted to 97.7–98.0 %. The total number of donations decreased by 6.0 % due to a significant decrease in the number of donations of automatic apheresis plasma (from 507,396 in 2016 to 388,742 in 2020, p < 0.001), at the same time, a significant increase in the number of donations platelets was noted (from 83,285 donations in 2016 to 126,574 in 2020, p < 0.001). During the follow-up period, there was an increase from 2.0 in 2016 to 2.21 in 2020 (10 %) in the average number of donations of blood components made by donors per year. Despite the decrease in the total number of donations in the analyzed period, the volume of blood components transferred for clinical use increased. The largest increase in blood components transferred at the request of medical organizations was noted for the concentrate of donor platelets (from 702,732 units in 2016 to 1,072,830 in 2020, by 34.5 %) and erythrocyte- containing blood components (from 491,791 liters in 2016 to 555,909 liters in 2020, by 13.5 %). A general trend was noted both towards a decrease in the frequency of detection of markers of bloodborne infections (from 16.8 to 7.7 %), and in individual infections. When analyzing the frequency of detection of infection markers, a significant difference was obtained in the group of newly registered and repeated donors (50,114 and 25,814, р < 0,001).Conclusion. The decrease of the number of cases of detection of infection markers and the redistribution of blood collection in accordance with the changing demands of medical organizations demonstrates a targeted strategy for improving the safety of transfusions, improving the quality of recruiting activities, and improving the principles of lean production of blood components.
Introduction. The new coronavirus infection COVID-19, fi rst detected at the end of 2019 in the Chinese city of Wuhan, caused a worldwide pandemic. High mortality among people with chronic diseases, a high frequency of the severe form of the disease, and an unspecifi ed number of asymptomatic carriers are all causes for heavy burden on the healthcare system, including the blood bank service. Aim – to assess the SARS-CoV-2 antibody formation in blood donors. Materials and methods. The research included test results for 12,314 blood samples of donors who donated blood during 04.29.2020 – 08.04.2021 at the National Medical Research Center for Hematology (Russia). Anti-RBD-SARS IgG were tested by «SARS-CoV-2-IgG-ELISA», manufactured by the National Medical Research Center for Hematology, LLC «HEMA» (Russia). Results. Among 12,314 blood samples from donors, 3,219 (26.14 %) were positive for antibodies to SARS-CoV-2. Antibodies detection rate increased from 8.52 to 58.09 % during the observation period. For representative evaluation of donors’ anti-SARS antibodies growth profi le, the results of detection were analyzed within two-week periods (including holidays). This approach made it possible to avoid counting the same donor twice. In the profi le of the growth of collective immunity in donors, two periods were identifi ed: May – November 2020 and November 2020 – April 2021. The period of May – November 2020 proved no signifi cant change in antibodies detection in donors. Detection rate was stable at about 15 % (13.10–16.24 %). The second period, from November 2020 to April 2021, demonstrated sustainable growth of this parameter from 16.20 to 58.09 %. This is likely due to the start of the second wave of COVID-19 in Russia (starting from November 2020) and an active campaign for mass vaccination that started in December 2020. To assess the true rate of increase of specifi c immunity in donors, the frequency of primary detection of antibodies to SARS-CoV-2 in donors in relation to those donors in whom antibodies were detected earlier was analyzed. The contribution of cases of primary detection of antibodies to SARS-CoV-2 was wave-like and corresponded to the epidemiological situation. Conclusion. An increase in the frequency of detection of antiviral antibodies in gratuitous blood donors was found during the spread of the second wave of COVID-19 and the n the beginning of mass vaccination. The increase in the overall frequency of antibody detection was due to donors with newly and re-detected antibodies. The surge in the frequency of primary detection of antibodies in blood donors corresponded to the second wave of infection.
Cytomegalovirus infection is one of the critical and life-threatening infectious complications in patients after allogeneic hematopoietic stem cell transplantation. The most significant risk factors for the development of cytomegalovirus infection are cytomegalovirus serostatus of the donor and recipient and delayed reconstitution of cytomegalovirus-specific CD4+ and CD8+ T lymphocytes after allogeneic hematopoietic stem cells transplantation. The infection may be asymptomatic or may lead to serious complications such as cytomegalovirus disease, which happens in 10-40% of cases. Cytomegalovirus infection has different impact on patients after hematopoietic stem cell transplantation. For instance, acute and chronic graft versus host disease may also be the risk factors for the development of cytomegalovirus infection. There is also information about the influence of cytomegalovirus infection on a graft failure. We also know that cytomegalovirus replication is associated with lower relapse risk in patients with acute myeloid leukemia and chronic myeloid leukemia. Antiviral prophylaxis and preemptive therapy are good strategies to reduce the risk of the cytomegalovirus infection. Despite this, cytomegalovirus infection is still associated with decreased overall survival and increased non-relapse mortality in recipients of allogeneic stem cells. The aim of this review is to systematize modern concepts used in the management and treatment of cytomegalovirus infections in patients after hematopoietic stem cell transplantation.
Aim. To assess the detection rate of human herpes virus DNA (of cytomegalovirus, herpes simplex virus types 1 and 2 [HSV-1/2], human herpes virus type 6 [HHV-6], and Epstein-Barr virus) in different biological environments at different stages of autologous hematopoietic stem cell transplantation (auto-HSCT) as well as the effect of immune factors on reactivation of viruses under study. Materials & Methods. From 2019 to 2021 the study enrolled 87 lymphoma patients during and after auto-HSCT. Virological monitoring was performed on biological fluids (blood, saliva, urine, etc.) prior to conditioning regimen on Day 0 as well as on Day +5 and Day +10 after auto-HSCT. On these days (Day 0, Day +5, and Day +10) the immune factors (IgM, IgG, and IgA levels and pattern of lymphocyte subpopulation in peripheral blood) in 15 % (14/87) of patients were assessed in terms of their effect on herpes virus reactivation. Results. The overall rate of viral DNA detection increased from 26 % (26/87) to 42 % (37/87) of cases in the period of granulocytopoietic recovery. The most frequent were HHV-6 and HSV-1/2 reactivations reported in 23 % (20/87) and 16 % (14/87) of cases, respectively. The median B-lymphocyte proportion in peripheral blood of patients with herpes virus reactivation was 0.26 %, whereas in patients without reactivation it was 6.7 % (p = 0.019). The median absolute B-lymphocyte count in the cohort of patients with detected viral DNAs was 0.001 x 109/L, whereas in patients without them it was 0.098 x 109/L (p = 0.026). Conclusion. A high rate of herpes virus DNA detection in lymphoma patients after auto-HSCT affected neither transplant engraftment nor transplantation mortality. Immune predictors of virus infection reactivation were the decreasing proportion of B-cells in the total lymphocyte count and the absolute B-lymphocyte count in the peripheral blood prior to auto-HSCT.
Introduction. Infection caused by cytomegalovirus (CMV) is a serious problem for patients with weakened immunity, including patients with hematopoietic depression. The cases of complications associated with cytomegalovirus require antiviral therapy. However, during the natural mutation process, especially with prolonged use of drugs in suboptimal doses, CMV strains resistant to the action of antiviral drugs (such as ganciclovir, valganciclovir) may occur. Hypothetically, the emergence of resistance in the virus may cause a more aggressive course of infection, the ineffectiveness of antiviral therapy and, as a result, an increase in the number of deaths. In this regard, timely detection of mutations that can potentially lead to the resistance of the virus to antiviral drugs during hematopoietic stem cell transplantation (HSCT), as well as during organ and tissue transplantation, may be important when making a therapeutic decision. We describe three clinical cases for which the dynamics of the appearance of a mutant strain of CMV by the UL97 gene, which correlates with the viral load and clinical picture, is analyzed.The aim of the study was to determine the timing of the occurrence of mutations in CMV phosphotransferase UL97 gene associated with resistance to antiviral drugs in patients with hemoblastoses after allogeneic hematopoietic stem cell (allo-HSCs) transplantation.Material and methods. The study included 48 samples of CMV DNA isolated from the peripheral blood of three allo-HSCs recipients with CMV infection who were treated in the clinics of the FSBI «National Medical Research Center for Hematology» of the Ministry of Health of Russia with oncohematological diseases during 2015–2017. Patients received conditional codes (PR, PD, and FS). Mutations associated with antiviral therapy (AVT) resistance were identified in all patients. Sanger sequencing was used for mutation detection. The obtained DNA sequences were analyzed using Nucleotide BLAST and Genome compiler software. Mutations were searched in MRA mutation resistance analyzer software. The nucleotide sequences were compared with the UL97 reference sequence of the Merlin CMV strain using this software environment.Results and discussion. For all patients in whom the virus strains containing C592G (PR), C607F (PD) and C603W (FS) mutations were detected, the timing of the mutation occurrence was determined at days 187, 124 and 1184, respectively. The emergence of mutations with a high resistance factor was shown to be accompanied by an increase in viral load (VL), the appearance of a clinical picture characteristic of CMV infection and a lack of an adequate response to therapy with ganciclovir and its derivatives.Conclusion. Using these results, it is proposed to develop the test system based on random polymerase chain reaction (rPCR) to detect mutations in the most frequently encountered codons: M460I/V, C592G, A591V, A594T/V, L595F/S, C603W. Given that the data on the prevalence of these mutations were obtained from foreign sources, it is advisable to conduct similar studies on the frequency of mutations in the UL97 gene among the population of the Russian Federation in order to improve the quality and accuracy of test systems.
Immunosuppressive treatment during the first year after renal transplantation leads to viral infection development in recipients, and graft dysfunction up to its loss. This original article gives data on comparison of T-lymphocytes subsets in healthy blood donors and renal graft recipients before and one month after transplantation. The influence of T-cell immunity impairment on CMV- and EBV-infection emergence were evaluated. 19 renal graft recipients were included in the study (average age — 43, m/f ratio — 14/5). 20 healthy blood donors were used as controls. A month after transplantation during induction (Methylprednisolone and Basiliximab) and basis (Prednisolone, Tacrolimus, Mycophenolate mofetil) therapy 10 (53%) patients had makers of CMV replication and 7 (36.9%) patients had markers of EBV replication. The majority of CMV- and EBV-positive patients proved reactivation of endogenous CMV and EBV (not primary infection). All patients, subsequently positive for CMV and EBV, demonstrated T-cells subpopulations discount before transplantation, such as a decrease in the total number of lymphocytes and absolute number of naïve CD4+ and СD8+ cells, effector memory CD4+ cells, T-regulatory cells (CD4+/CD25+/CD127–) in comparison to the control group. EBV-positive patients also showed the reduction of CD3+, absolute number of CD4+ and CD8+, but central memory CD8+ cells increased in comparison to the control group. Viral reactivation rate during first month after renal transplantation depends not only on immunosuppressive regimen but on T-cells subsets disproportions before graft. These indicators could be taken into account for viral infection expectancy.
Introduction. The achievement of the goal of the World Health Organization to eliminate viral hepatitis B by 2030 seems to be problematic partly due to the presence of escape mutants of its etiological agent, hepatitis B virus (HBV) (iHepadnaviridae: Orthohepadnavirus: Hepatitis B virus/i), that are spreading mainly in the risk groups. Specific routine diagnostic assays aimed at identification of HBV escape mutants do not exist.The study aimed the evaluation of the serological fingerprinting method adapted for routine detection of escape mutations in 143 and 145 aa positions of HBV surface antigen (HBsAg).Material and methods. HBV DNA from 56 samples of HBsAg-positive blood sera obtained from donors, chronic HBsAg carriers and oncohematology patients has been sequenced. After the identification of mutations in HBsAg, the samples were tested in the enzyme-linked immunosorbent assay (ELISA) kit «Hepastrip-mutant-3K».Results and discussion. Escape mutations were detected mainly in patients with hematologic malignancies. Substitutions in 143 and 145 aa were found in 10.81% and in 8.11% of such patients, respectively. The G145R mutation was recognized using ELISA kit in almost all cases. The kit specifically recognized the S143L substitution in contrast to the S143T variant. The presence of neighbor mutation D144E can be assumed due to it special serological fingerprint.Conclusion. ELISA-based detection of escape mutations S143L, D144E and G145R can be used for routine diagnostics, especially in the risk groups. The diagnostic parameters of the kit can be refined in additional studies. This immunoassay and methodology are applicable for the development and quality control of vaccines against escape mutants.
The review provides information on the mechanisms of the emergence of resistance to antiviral drugs in human viruses from the subfamily Betaherpesvirinae. Data on the principles of action of antiviral drugs and their characteristics are given. The occurrence rates of viral resistance in various groups of patients is described and information about the possible consequences of the emergence of resistance to antiviral drugs is given. Information is provided regarding the virus genes in which mutations occur that lead to viral resistance, and a list of such mutations that have described so far is given. The significance of the study of mutations leading to the resistance of the virus to antiviral drugs for medical practice is discussed.
Objective. To determine type of cytomegalovirus (CMV) infection (reactivation of a virus strain that was present before transplantation or re-infection with another virus strain) in allogeneic hematopoietic stem cell recipients by sequencing. Materials and Methods. Clinical and laboratory data of 179 recipients of allogeneic hematopoietic stem cells collected from 2014 to 2018 were analyzed for CMV DNA in clinical specimens before and after transplantation. A total of 14 patients (28 samples) were included in the study. The CMV UL139 gene encoding viral glycoprotein was chosen for virus genotyping and sequence alignment. The primers complementary to its conservative sites were used. The resulting DNA sequence was analyzed using nucleotide BLAST software (https://blast.ncbi.nlm.nih.gov/Blast.cgi) and Genome compiler (https://designer.genomecompiler.com). The type of infection was determined by comparing DNA sequences before and after transplantation. Results. All enrolled patients were anti-CMV-positive prior to transplantation, which indicates the presence of CMV infection. Therefore, none of the patients had a primary infection as a result of transplantation. Of 14 patients, high percentage of sequence alignment (~100%) was observed in 8 patients. For the other 6 patients, substantial differences in sequences which indicate the different genotypes and the different type of infection were found. However, there was no statistically significant difference in the time to viral DNA appearance after transplantation in patients with re-infection and reactivation (p > 0.05), nor was there a statistically significant correlation between the type of infection (reactivation/re-infection) and the main diagnosis or transfusion load. Conclusions. Reactivation of the previously registered viral strain and re-infection with another viral strain were equally probable (8 vs. 6 cases). There were no associations between the main diagnosis and the type of infection (reactivation/re-infection) possibly due to a small sample size. Time to post-transplantation CMV DNA detection in blood was longer for re-infection (median of 69.5 days) compared to reactivation (median of 27 days), but this difference was also non-statistically significant. In addition, there was no significant contribution of blood transfusion burden to the type of CMV infection, which may suggest the donor blood is not a source of the different strains.
Introduction. The SARS-CoV-2 infection (COronaVIrus Disease 2019, COVID-19) usually progresses uncomplicated in an acute respiratory form but causes frequent severe illness in oncohaematological patients.Aim — analysis of the management and efficacy of medical aid at a haematology clinic during the COVID-19 pandemic.Patients. The clinic admitted 2,130 patients in April 20 — November 20, 2020, with 920 of them triaged into observatory wards. At the time of admission, 907 (98.5 %) patients were SARS-CoV-2 RNA-negative, with 13 hospitalised without nasopharyngeal swab tests. Patient nosology: 235 (25.5 %) lymphoma, 152 (16.5 %) multiple myeloma, 131 (14.2 %) acute leucaemia, 86 (9.3 %) haemophilia, 35 (4 %) Gaucher’s disease, 17 (1.8 %) Waldenstrom macroglobulinemia, 16 (1.7 %) aplastic anaemia, 153 (16.6 %) various surgical diseases, 81 (8.8 %) other haematological diseases and 14 (1.6 %) were bone marrow donors.Results. Among the 920 patients admitted to the observatory, 139 (15 %) were severe and 653 (71 %) had a moderate condition. Fever was reported in 124 (13.5 %) patients at admission. Chest computed tomography (CT) was performed in 809 patients, with recent lung inflammation detected in 121 (15 %) cases. Twenty four (2.6 %) patients were revealed SARS-CoV-2-positive, with 20 diagnoses PCR-verified and four — in chest CT. Ten patients were diagnosed positive in routine examination or at a specialty unit as fever aggravated. Thus, a two-staged SARS-CoV-2 screening with PCR and chest CT allowed an extra 2.6 % detection of COVID-19 cases despite negative tests at admission.Conclusion. The observatory management has reduced the likelihood of nosocomial COVID-19 and ensured a continued supply of specialty medical aid.
Introduction. Occult hepatitis B virus (HBV) revelation in HBV nuclear antigen testing is of particular importance to prevent transfusion infection. Aim - the identification of factors affecting the anti-HBc detection rate in donated transfusable blood components from different regions of Russia. Materials and methods. A cohort screening single-stage epidemiological study was conducted with 2,000 donor blood samples, 500 samples per each of four regions of the country, the Republics of Crimea (Simferopol) and Sakha (Yakutia), the cities of Saransk and Orenburg. Data on 968 blood samples from the National Research Center for Hematology's donor bank were used as reference. The testing targeted HBV nuclear antigen antibodies. Positive donated blood samples were additionally tested for IgM and virus surface antigen antibodies using Abbott and Vector-Best commercial reagent kits. Results. Donor demographic profiles differed insignificantly across members of the Russian Federation. Males predominated among the donors (69.6%). Anti-HBc was detected in 219 of 2,000 samples examined (10.9%). The donor blood sample anti-HBc detection rate ranged from 6.0 to 21.6%, depending on the region. Anti-HBc-positive proportions in Orenburg, Crimea, Mordovia and Sakha comprised 8.2, 8.0, 6.0 and 21.6%, respectively (p < 0.01). First-time donors had anti-HBc in 8.06, regular donors - in 11.29% cases. The anti-HBc detection rate varied with donor's age, being zero or near 1% in 20-yo or younger people. Acute HBV antibodies had zero rate in Orenburg at zero or low-titre (< 100 mIU/mL) protective antibodies; 31 total samples, 15 low-titre and 16 negative for protective antibodies. In Simferopol, acute phase antibodies were negative in 7 blood samples containing high-titre protective antibodies (> 100 mIU/mL) and in 5.0% samples with their low or zero levels. In Yakutian donors, acute phase antibodies were revealed only at protective antibodies negative. In Saransk, this marker was equal-proportion at zero and high-titre protective antibodies (3.3% each). Conclusion. Transfusion component procurement from younger donors should be prioritised as enhancing haemotransfusion viral safety. Positive occult HBV tests were less common in regions with low HBV incidence.
Purpose: to justify the need to use at least two methods (direct and indirect) for reliable laboratory decoding of infectious mononucleosis. Materials and methods. We observed 107 children with infectious mononucleosis. Deciphering the etiology was carried out using ELISA (We determined IgM VCA-EBV, IgG EA-EBV, IgG EBNA-EBV, IgM CMV, IgG CMV in serum) and PCR (We determined investigated viral DNA (EBV, CMV, HHV 6) in peripheral blood mononuclear cells). Results: In the structure of infectious mononucleosis, EBV remains the leading infection: 82 children (76.6%). In case of reactivated EBV infection, the isolated use of the ELISA method does not limit the possibility of interpreting the results without additional evaluation of the test results by PCR. A significantly level of viral DNA concentration in the examined children has not been established. The detection frequencies of EBV DNA and HHV 6 DNA by PCR are not mutually independent (p < 0.001). Detection of one of the viruses reduces the chance of detecting another virus (OR = 0.133; 95% CI from 0.0537 to 0.3273, p < 0.0001).