Changes in the cytotoxic and regulatory functions of NK cells in patients with long-COVID under the influence of the human herpesvirus 6 (pilot study).

Long-COVID are often accompanied by the development of autoimmun disorders. Such dysregulation of the immune system can be caused by reactivation of "sluggish" herpesvirus infection in patients after COVID-19. The one of the possible causes of autoimmunization is a change in the cytotoxic functions of NK cells under the influence of HHV6. The aim of research was to study the expression of receptor-ligand Fas-FasL, regulating marker CD38 and inhibitory receptor TIM-3 on NK cells in patients with long-COVID after mild, moderate, and severe stage of COVID-19 in the anamnesis with or without reactivation of HHV-6 and to identify risk factors for the formation of autoimmune disorders in these patients. This study investigated 124 adults (73 female and 51 male) aged 18 to 65 years with long-COVID. The groups of patients with long-COVID were divided depending on mild, moderate, and severe forms of COVID-19 in the anamnesis and with/without reactivation of HHV-6. The control group included 20 healthy participants. Molecular genetic studies (PCR) were performed for all patients to detect the existence of DNA HHV6. Multiparametric flow cytometry was performed on 124 EDTA peripheral blood samples collected from long-COVID patients and 20 healthy controls. There was defined an imbalance between acute antiviral mechanisms, the response contributing to tissue damage and immunopathology, probably autoimmunity in patients with long-COVID after different forms of COVID-19 with reactivation of HHV-6. The presence of HHV-6 in groups with long-COVID was accompanied by higher expression of FasL and CD38, especially in patients, who had a severe form of COVID-19 in the anamnesis. The decrease in TIM-3 in patients with reactivation of HHV-6 compared to patients without HHV-6 puts the preservation of immunological tolerance at risk of Th1-dependent immune responses. The reactivation of HHV-6 is accompanied by higher expression of FasL and CD38, which indicates increased hyperactivation of NK cells, their cytotoxic activity, and subsequent exhaustion. NK cells of these patients lose their immunoregulatory ability, this creates prerequisites for the development of immunopathology, probably autoimmune processes.

EFFICACY OF PRIMARY REHABILITATION MEASURES ASSOCIATED WITH THE DEVELOPMENT OF RECURRENT BRONCHIAL OBSTRUCTION SYNDROME IN YOUNG CHILDREN WITH RESPIRATORY DISORDERS IN NEONATAL PERIOD.

OBJECTIVE: The aim: To improve primary prophylactic measures associated with the development and progression of recurrent bronchial obstruction syndrome in young children, who had suffered respiratory disorders in neonatal period. PATIENTS AND METHODS: Materials and methods: Algorithm of primary prophylactic measures implied adequate balanced nutrition, sanation of living conditions, restriction of contact with infectious agents, sanation of chronic foci of infection, systematic training and general fitness. The investigation included 160 young children (1 day - 3 years of age). The basic group (n=80) involved children, who had experienced respiratory disorders in neonatal period and received appropriate respiratory therapy (artificial ventilation and / or spontaneous breathing with continuous positive airway pressure and supply of free oxygen), control group - children, who did not have respiratory disorders and respiratory therapy (n=80). RESULTS: Results: Conducted investigation throughout 12-month monitoring enabled to record the development of recurrent bronchial obstruction syndrome in 43 children (respectively, 30 - 37.50% patients of the basic group versus 13 - 16.25% of control group; p 0.05), could not be obtained. CONCLUSION: Conclusions: Comparative analysis within groups did not show a reliable difference in the development of recurrent bronchial obstruction syndrome in children (р>0.05), which can be explained by partial following of doctor's recommendations. There is the need in further study of the issue involving more patients for a longer period of monitoring.

Herpesvirus infections and post-COVID-19 manifestations: a pilot observational study.

The global spread of SARS-CoV-2 points to unrivaled mutational variation of the virus, contributing to a variety of post-COVID sequelae in immunocompromised subjects and high mortality. Numerous studies have reported the reactivation of "sluggish" herpes virus infections in COVID-19, which exaggerate the course of the disease and complicate with lasting post-COVID manifestations CMV, EBV, HHV6). This study aimed to describe clinical and laboratory features of post-COVID manifestations accompanied by the reactivation of herpes virus infections (CMV, EBV, HHV6). 88 patients were recruited for this study, including subjects with reactivation of herpes viruses, 68 (72.3%) (main group) and 20 (27.7%) subjects without detectable DNA of herpesviruses (control group): 46 (52.3%) female and 42 (47.7%) male; median age was 41.4 ± 6.7 years. Patients with post-COVID manifestations presented with reactivation of EBV in 42.6%, HHV6 in 25.0%, and EBV plus HHV6 in 32.4%. Compared with controls, patients with herpes virus infections presented with more frequent slight fever temperature, headache, psycho-neurological disorders, pulmonary abnormalities and myalgia (p < 0.01), activation of liver enzymes, elevated CRP and D-dimer, and suppressed cellular immune response (p ≤ 0.05). Preliminary results indicate a likely involvement of reactivated herpes virus infections, primarily EBV infections in severe COVID-19 and the formation of the post-COVID syndrome. Patients with the post-COVID syndrome and reactivation of EBV and HHV6 infections are at high risk of developing various pathologies, including rheumatologic diseases.

Allergen component testing - a new era in diagnostics of patients with pollen allergy.

OBJECTIVE: Introduction: Pollen allergy, also called hay fever or pollinosis, is referred to the most widespread allergic diseases. According to different sources, from 5 to 34% of the population in developed countries are likely to suffer from this condition. Moreover, the majority of patients are young people of working age The aim: To demonstrate a practical decision of the choice of effective treatment tactics based on component testing in patients with pollen allergy. PATIENTS AND METHODS: Materials and methods: 126 рatients with allergic rhinitis / conjunctivitis were randomly selected according to their primary visit during the first week in August of the current year. Among them, 53 (42.0%) female and 73 (58.0%) male, aged 22-47 years. General laboratory and instrumental investigations, skin prick test with allergen extracts (Diater, Spain), measurement of total serum and specific IgE by immunoenzymatic assay method using test system "Euroimmun" were performed. Immunofluorescent methodImmunoCap (Thermo Scientific, Uppsala, Swiss) was used to detect specific components of allergens. The material of investigation was blood serum. RESULTS: Results: According to the results of skin prick-test, 50% of patients could receive allergen immunotherapy with two different extracts of allergens "Mixture of Weeds" and "Mixture of Grass". On molecular investigations, it was detected that this combination was not suitable for any patient (20% of individuals had genuine sensitization to allergens of grass pollen, including a marker of cross-reactive molecules, 30% of individuals were sensitized with genuine allergens of Artemisia and/or ambrosia). CONCLUSION: Conclusions: Based on skin prick-test and molecular diagnostics, the doctor makes a completely different decision on the choice of extracts for allergen immunotherapy conduction. Component determination of a sensitized profile and high sensitivity of this method enables to reveal a genuine protein, which is the primary cause of allergy occurrence and administer etiotropic allergen-specific immunotherapy with the allergen, to which sensitization was detected.

Low Level of Advanced Glycation End Products in Serum of Patients with Allergic Rhinitis and Chronic Epstein-Barr Virus Infection at Different Stages of Virus Persistence.

Advanced glycation end products (AGEs) are formed in a nonenzymatic reaction of the reducing sugars with amino groups of proteins, lipids, and nucleic acids of different tissues and body fluids. A relatively small number of studies have been conducted on the role of AGEs in allergic inflammation. In this study, patients with allergic rhinitis (AR) were examined for the presence of Epstein-Barr virus and the content of fluorescent and nonfluorescent AGEs. We have also determined the level of a unique epitope (AGE10) which was recently identified in human serum using monoclonal antibodies against synthetic melibiose-derived AGE (MAGE). The levels of AGE10 determined with an immunoenzymatic method revealed no significant difference in the patients' blood with intermittent AR and chronic EBV persistence in the active and latent phases. It has been shown that there is a statistically significantly smaller amount of AGEs and pentosidine in groups of patients, both with and without viremia, than in healthy subjects. In turn, higher levels of immune complexes than of AGE10 were detected in the groups of patients, in contrast to the control group, which had lower levels of complexes than AGE10 concentration. In patients with active infection, there is even more complexes than of noncomplexed AGE10 antigen. The lower level of AGE in allergic rhinitis patient sera may also be due, besides complexes, to allergic inflammation continuously activating the cells, which effectively remove glycation products from the body.