CELL-MEDIATED AND HUMORAL IMMUNITY DURING COVID-19 IN THE REPUBLIC OF CRIMEA

The COVID-19 (coronavirus disease 2019) pandemic has spurred the development ofhighly effective quantitative methods for assessing the adaptive immune response to the SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus 2) virus. In order to assess the humoralcomponentofthe immune response, various methods for detecting immunoglobulins A, M, Gare widely used. ELISPOTseems to be the most accessible and effective method to assess the level of T cells that specifically respond to the SARS-CoV-2 virus antigens. The aim. To assess cell-mediated and humoral immunity in COVID-19 in residents of the Republic of Crimea. Methods. The study was performed on 24 volunteers: the presence of coronavirus antibodies was determinedby ELISAmethod, andthe presence ofcontact withcoronavirus proteins - by the ELISPOT "TigraTest® SARS-CoV-2” method (Generium, Russia). For retrospective study of humoral immunity in the population, we assessed 10 000 ELISA tests (ECOlab IgM and IgG, Russia) performed in our laboratory for the period from July 2020 to January 2022. Results. The results show the effectiveness of using the ELISPOT method to detect latent forms of coronavirus infection. It is important to note that there is statistically significant relationship between the timing of the disease and the number of spots in both antigen panels. After vaccination against SARS-CoV-2, cell-mediated immunity lasts up to 6 months or more. Conclusions. As a result of the study, it was found that during 2021, the level of immunization of the population of the Republic of Crimea against COVID-19 has significantly increased;the proportion of residents who have positive IgG test has increasedfrom 27%to 87%. The results ofELISPOTstudies using a setofreagents for in vitro detection ofbloodT-lymphocytes thatspecifically respondto SARS-COV-2 virus antigens ("TigraTest® SARS-CoV-2”) showed that this method is more sensitive than ELISA in detecting latent diseases. © 2023 Voprosy Literatury. All rights reserved.

The Clinical Case: Covid-19 in a Child with Chronic Kidney Disease

Since the spread of the novel coronavirus infection, most researchers have noted a low proportion of sick children in general pediatric cohort compared to adults, who had a mild disease course and rare complications. The most frequent clinical manifestations of the disease are respiratory and, some less frequently diarrheal syndromes. The disease has predominantly mild or asymptomatic course. The risk of adverse outcomes in children, similar to adults, clearly correlate with the presence of background chronic pathology. The need for respiratory support prevails in children with a severe premorbid burden. Here, a clinical case of ongoing novel coronavirus infection in adolescent patient comorbid with chronic kidney pathology is described. In adolescence, the patient was diagnosed with mesangioproliferative glomerulonephritis (IgA-nephropathy), and further registered at the dispensary receiving a combination therapy with angiotensin converting enzyme inhibitors and disaggregation drugs. The epidemiological history contained no established contacts with infectious patients. The clinical manifestations of COVID-19 in the patient are represented by catarrhal and diarrheal syndromes, transient renal dysfunction in the acute period of the disease. The onset of coronavirus infection was clinically characterized by symptoms of damaged gastrointestinal tract and was considered as acute gastroenteritis of infectious etiology. Empirically prescribed antibacterial therapy in combination with antiplatelet agents and symptomatic drugs had no effect. The diagnosis of the novel coronavirus infection was verified only on day 4 of hospitalization, clinical and laboratory signs of lung damage emerged. The inflammatory process developed in the patient lungs was secondary to the main pathology. The severity of the patient's condition was determined by the presence of respiratory and renal insufficiency. Lung damage with minimal severity complaints and clinical data had a bimodal pattern and required respiratory support. A comprehensive approach to treatment, including respiratory, antiviral, enterosorption, anticoagulation, anti-inflammatory, antihypertensive, hepatoprotective, symptomatic therapy with change in antibacterial drugs allowed to achieve positive dynamics. On day 12 of the illness, the patient required no respiratory support. The presence of symptoms of gastrointestinal tract damage in COVID-19 necessitates the mandatory inclusion of PCR assay for SARS-CoV-2 into diagnostic protocol in patients with diarrheal syndrome to perform etiological disease interpretation.

ELISPOT ASSAY OF THE SARS-COV-2 SPECIFIC T CELLS IMMUNE RESPONSE

The COVID-19 pandemichas stimulate dinterestin the developmen to fbiotechnology, as well as in the search for new solutions in the diagnostics of immune processes. The response of immunoglobulins A, Mand Ghada significantrole in the assessment of virus-specific immune responses. Later, it was understood that for a comprehensive assessment of adaptive immunity processes, it is reasonable to study its cellular component. One of the most affordable methods for assessing T cell immunity, which has proven itself in the diagnosis of other infectious diseases, such as latent tuberculosis infection, is IGRA ELISPOT. The aim of the study. To determine SARS-СoV-2 specific immune response ofT lymphocytes in vitro in the peripheral blood of volunteers from various groups using IGRA ELISPOT method. We evaluated the applicability of the method to assess T cell immune response to infection andvaccination. In addition, we determinedthe duration of the maintenance period of the SARS-CoV-2 specific T cells immune response induced by vaccination. Materials andmethods. The study was carriedout on venous bloodsamples ofvolunteers from three groups: 1) hospital patients withCOVID-19;2) COVID-19convalescents;3) vaccinatedagainst COVID-19. The T cellimmune response was assessed using the TigraTest® SARS-CoV-2 test system, which determines in vitro the number of T cells secreting interferon-gamma in response to stimulation with SARS-СoV-2 peptides in two antigens panels: 1) peptides of the spike protein (S);2) peptides of N, M, Orf3a and Orf7a proteins. Conclusion. The IGRA ELISPOT assay is a specific and sensitive tool in the assessment of T cell immunity to the SARS-CoV-2 virus. The method makes it possible to assess SARS-CoV-2 specific T cell responses induced both by natural encounter with the pathogen and by vaccination. It is advisable to use the method in routine practice for comprehensive assessment of immunity to SARS-CoV-2. © 2022 Acta Biomedica Scientifica. All rights reserved.

Sorrelation between age and the intensity of the post-vaccination humoral immune response in individuals passed COVID-19

Introduction. Despite widespread vaccination against COVID-19 worldwide, the epidemiological situation remains insufficient. The appearance of mutant forms of SARS-CoV-2 with increased virulence causes new waves of COVID-19 morbidity. The virus variability can cause the reduction of the vaccination effectiveness. In this regard, it is important to study the dynamics of post-vaccination immunity, its features in various population groups, as well as the relationship between post-infectious and post-vaccination immunity. The study continues a series of researches of the features of SARS-CoV-2-specific immunity in COVID-19 convalescents and recipients of the <<Sputnik V>> vaccine. The aim of the study - assessment of the intensity of the SARS-CoV-2-specific immune response in different age groups of people passed COVID-19 and subsequently vaccinated with <<Sputnik V>>. Material and methods. With the help of EIA, the level of IgG antibodies to S-antigen and N-antigen of SARS-CoV-2 was studied in 155 samples of blood sera of individuals (men and women) aged 18 to 70 years who passed COVID-19 and after 6 month of recovery underwent a full course of vaccination with <<Sputnik V>>. Samples from individuals of the following age groups were examined: from 18 to 35, from 35 to 45, from 45 to 55, from 55 to 65, from 65 to 70 years. Results. In all the examined age groups of individuals passed COVID-19 and then vaccinated with <<Sputnik V>>, there was a high level of IgG antibodies to SARS-CoV-2 S-protein (positivity coefficient 8.1 and higher). The level of IgG antibodies to the N-protein in more than half of the cases was lower than positive values among all the subjects. Conclusion. The study showed that individuals passed COVID-19 and then vaccinated with <<Sputnik V>>, regardless of age, have intense post-vaccination humoral immunity. Copyright © 2022 Meditsina Publishers. All rights reserved.

TREC and KREC as prognostic markers of HIV infection and COVID-19

In some infectious diseases, the number of T- and B-lymphocytes is significantly reduced which is associated with a high risk of the disease progression. The article reviews the effect of two RNA-containing viruses on the specific immune system: SARS-CoV-2 and HIV, as well as parameters of T- and B-cell neogenesis of TREC and KREC, which are markers of immunological disorders and can be used for prognosis for these infections. © 2022 New Terra Publishing House. All rights reserved.

The potential of Pathogenetic Therapy in the Treatment of New Coronavirus Infection COVID-19

The objective: to increase efficacy of treatment of patients with new coronavirus infection COVID-19 by prescription of Remaxol. Subjects and Methods: 105 patients with confirmed new coronavirus infection COVID-19 with lung damage from 25 to 50% (CT-2) were examined and divided into 2 groups (Main Group and Comparison Group). All patients received standard treatment;patients from Main Group (55 people) additionally received Remaxol intravenously 200.0 ml No. 10 daily, then No. 5 every other day. Treatment efficacy was assessed between the 3rd and 4th week of the study. Results: the patients treated with Remaxol showed more pronounced positive changes of clinical and laboratory symptoms (lower frequency of fever, improved state of health, appetite, decreased dyspnea, cough and wheezing, higher level of SpO2, decreased neutrophilia and blood clotting, ferritin levels, a significant increase in activity of superoxide dismutase in erythrocytes and a decrease in myeloperoxidase activity in neutrophils) versus patients receiving standard treatment. The CT lung scan after 3 weeks in patients from Main Group showed the transformation of ground-glass areas into impactions according to the consolidation type in 58.2% (32 people), in 52.2% (29 people) there appeared an organizing pneumonia, a decrease in size of impactions was observed in 54.6% (30 people);in Comparison Group - in 24.0% (12 people), 20% (10 people) and 24% (12 people), respectively, in all three comparisons (p < 0.05). Copyright© 2022 Klinicheskaya Onkogematologiya/Clinical Oncohematology. All rights reserved.

THE CLINICAL CASE: COVID-19 IN A CHILD WITH CHRONIC KIDNEY DISEASE

Since the spread of the novel coronavirus infection, most researchers have noted a low proportion of sick children in general pediatric cohort compared to adults, who had a mild disease course and rare complications. The most frequent clinical manifestations of the disease are respiratory and, some less frequently diarrheal syndromes. The disease has predominantly mild or asymptomatic course. The risk of adverse outcomes in children, similar to adults, clearly correlate with the presence of background chronic pathology. The need for respiratory support prevails in children with a severe premorbid burden. Here, a clinical case of ongoing novel coronavirus infection in adolescent patient comorbid with chronic kidney pathology is described. In adolescence, the patient was diagnosed with mesangioproliferative glomerulonephritis (IgA-nephropathy), and further registered at the dispensary receiving a combination therapy with angiotensin converting enzyme inhibitors and disaggregation drugs. The epidemiological history contained no established contacts with infectious patients. The clinical manifestations of COVID-19 in the patient are represented by catarrhal and diarrheal syndromes, transient renal dysfunction in the acute period of the disease. The onset of coronavirus infection was clinically characterized by symptoms of damaged gastrointestinal tract and was considered as acute gastroenteritis of infectious etiology. Empirically prescribed antibacterial therapy in combination with antiplatelet agents and symptomatic drugs had no effect. The diagnosis of the novel coronavirus infection was verified only on day 4 of hospitalization, clinical and laboratory signs of lung damage emerged. The inflammatory process developed in the patient lungs was secondary to the main pathology. The severity of the patient’s condition was determined by the presence of respiratory and renal insufficiency. Lung damage with minimal severity complaints and clinical data had a bimodal pattern and required respiratory support. A comprehensive approach to treatment, including respiratory, antiviral, enterosorption, anticoagulation, anti-inflammatory, antihypertensive, hepatoprotective, symptomatic therapy with change in antibacterial drugs allowed to achieve positive dynamics. On day 12 of the illness, the patient required no respiratory support. The presence of symptoms of gastrointestinal tract damage in COVID-19 necessitates the mandatory inclusion of PCR assay for SARS-CoV-2 into diagnostic protocol in patients with diarrheal syndrome to perform etiological disease interpretation.

Post-vaccination and post-infection humoral immune response to the SARS-CoV-2 infection

Introduction. Mass vaccination of the population against SARS-CoV-2 in Russia and abroad has been going on for more than 2 years. Various types of vaccines are used for vaccination (vector vaccines, RNA vaccines, whole-virion vaccines). The first in the world was registered the Russian vector vaccine «Gam-COVID-Vac» («Sputnik V»), which is widely used in our country, as well as in many other countries of the world. An important area of research is the monitoring of the parameters of the vaccine-induced immune response their analysis in relation to the characteristics of the immune response caused by SARSCoV-2 infection/COVID-19. Such studies are important both for assessing the intensity and duration of post-vaccination immunity, and for improving strategies for immunoprophylaxis and immunotherapy of coronavirus infection. The article presents the results of a study of the humoral immune response in patients with COVID-19 and vaccinated with «Sputnik V» in the period from autumn 2020 till the present time. The aim of the work - a comparative study of the humoral immune response to SARSCoV-2 infection and vaccination against COVID-19. Material and methods. The content of antibodies against SARS-CoV-2 S- and N-proteins was studied in 449 blood serum samples of men and women (age 25-65 years). 5 groups of samples were formed: suffered from COVID-19 of mild and moderate severity, at different times after recovery (262 samples);immunized with the «Sputnik V» vaccine, at different times after injection of the 2nd component of «Sputnik V» (104 samples);suffered from COVID-19 of mild and moderate severity, and then vaccinated with «Sputnik V» (53 samples);vaccinated with «Sputnik V», and then suffered with COVID-19 (12 samples);revaccinated with the vaccine «Sputnik Light» (18 samples). Results. To assess the content of IgG antibodies to S-protein and to N-protein of SARSCoV-2 in human blood sera, an EIA diagnostic system was developed further certified by the Ministry of Health of Russian Federation. In people suffered COVID-19 in 90 % of cases the positive levels of IgG antibodies to SARS-CoV-2 S-protein persist 9 months after recovery, while the proportion of potential plasma donors and material for obtaining intravenous immunoglobulin with a high content of IgG antibodies to S-protein 1 month after the disease is 20 %. In 76 % of people vaccinated with «Sputnik V» high levels of IgG antibodies to S-protein are detected within 6 months after the course of vaccination. The content of IgG antibodies to S-protein in the blood sera of persons suffered COVID-19, and then 6 months after recovery vaccinated with the 1st component of the vaccine «Sputnik V» in 100 % of cases was high with a positivity coefficient above 8.1, regardless of the initial value, already on 7 and 21 days after injection. In persons vaccinated with «Sputnik V» and then passed COVID-19, a high content of S-specific IgG antibodies is observed in 100 % of cases. The examination of vaccinated persons who underwent revaccination with «Sputnik Light» showed a 100 % high level of antibodies against S-protein. Conclusion. The developed test system may be suitable for assessing the content of IgG antibodies to SARS-CoV-2 antigens in COVID-19 patients, vaccinated and revaccinated. The performed study demonstrated that there is a intensive post-vaccination immunity for 6 months and post-infectious immunity for 9 months.

Complicated course of COVID-19 in a child with Bloch–Sulzberger syndrome

The authors describe a clinical case of a protracted course of a new coronavirus infection in a child with the development of severe complications against the background of a hereditary disease of neurocutaneous melanoblastosis, Bloch–Sulzberger syndrome. The progression and severity of the disease was caused by acute onset, lack of specific therapy at the onset of the disease and late seeking for medical help. For 2 months, the patient had long-term persistent SARS-CoV-2 viremia with the development of viral-bacterial pneumonia. A defect in the immune system in the early period of the disease contributed to the protracted course of the disease and the development of complications. The outcome of the disease in this patient was predetermined by the combination of etiological factors tropic to the respiratory system, the presence of background genetic pathology with the development of a pathological response of the innate and adaptive immune system of the body to massive replication of SARS-CoV-2 with the development of the late phase of COVID-19. © 2021 National Academy of Pediatric Science and Innovation. All rights reserved.

Tuberculosis under conditions of novel coronavirus infection

Tuberculosis (TB) remains an important medical and social problem up to today. In recent years, great strides have been made in the fight against tuberculosis infection (TI) in reducing TB morbidity and mortality, especially in the Russian Federation. Emergence of new COVID-19 infection in the world has led to the need for long-term isolation of the population, on the one hand, and the need to resort to personal protective equipment, on the other. The spread of COVID-19 may have an impact on the increase in TB morbidity, despite the decrease in the incidence rate, which is related to objective difficulties in detecting TB and complexity of the structure of clinical manifestations of the disease against the background of coronavirus infection and severe complications after COVID-19. The use of immunosuppressive therapy in the treatment of COVID-19 may cause immunosuppression, which will affect the results of TI immunodiagnostics using skin tests. At the same time, IGRA tests can be useful in these conditions, since they are of great diagnostic value. Equally important is the reduction of patient visits to treatment facilities in the context of a pandemic or a high incidence of COVID-19.

Immunotherapy in the treatment of covid-19

The high mortality rate in COVID-19 can be explained by the development of a hyperinflammatory syndrome, characterized by a cytokine storm and extensive thrombus formation. The main direction for preventing the development of hyperinflammatory syndrome and reducing mortality from COVID-19 is immune therapy, however, the data on the efficacy and criteria for prescribing immune drugs is very heterogeneous. The purpose of this review is to analyze the results of clinical trials on the use of various types of immune therapy and possible criteria for its prescription. Analysis of literature data showed that the most effective among the existing variants of immune therapy were monoclonal antibodies to IL-6, the use of donor plasma in the early stages of treatment. Janus kinase inhibitors, intravenous immunoglobulin improved the clinical characteristics of patients, but did not affect the mortality rate. An analysis of possible predictor-markers of the development of a cytokine storm revealed an increase in the number of neutrophils > 11 × 103/ml, a decrease in the number of lymphocytes > 1000 × 103/ml, an increase in the level of IL-6 > 24 pg/ml, LDH > 300 IU/L, D-dimer > 1000 ng/ml, and CRP > 10 mg/dL as the most informative and accessible in clinical practice at the moment.

Molecular immunological aspects of diagnostics, prevention and treatment of coronavirus infection

The rapid spread of the infection caused by the new coronavirus SARS-CoV-2, which in a short time covered almost the whole world and acquired the pandemic character, has become a serious challenge to the health care system. Unprecedented measures are being taken to organize medical care for infected people, carry out quarantine measures, develop drugs for treatment and prevention of infection. Over the past 2020 year a significant amount of scientific information has been accumulated about the pathogenesis of SARS-CoV-2 infection, the biology of the virus and its interaction with the human immune system. This made it possible to come close to the development of effective substances of countering the spread of a new coronavirus infection – the development of effective vaccines and innovative targeted antiviral drugs. This review is devoted to analysis of the latest advances in the diagnosis, immunoprophylactics and treatment of COVID-19, a disease caused by the novel SARS-CoV-2 coronavirus.

Dornase alfa in the treatment of COVID-19: Destruction of neutrophil extracellular traps

In the severe or fatal course of COVID-19, rapid virus replication gives rise to exuberant inflammatory response including cytokine storm, characterized by elevated plasma concentrations of proinflammatory cytokines that support neutrophil activity and stimulate endothelial cells. Рost mortem examinations confirm these data, indicating extensive neutrophil infiltration and accumulation of neutrophil extracellular traps (NET)s in lung tissues of patients who have died from COVID-19. In this paper the possibility of therapy with dornase-alfa in COVID-19 patients is discussed. Designed to treat cystic fibrosis lung disease, this drug can reduce neutrophil activity, slow down the NET release and accelerate the NET clearance in the airways of COVID-19 patients. The authors also present the protocol of COVID-19 therapy with dornase-alfa produced by Russian manufacturer.

BCG vaccination as protection from COVID-19: epidemiological and molecular biological aspects

The article presents a review of the recent hypothesis that the national policy of BCG-vaccination affects the spread of COVID-19 in different countries. It contains the information from 70 publications with epidemiological indicators, providing pros and cons of this hypothesis, with the description of possible mechanisms of non-specific antiviral action of BCG vaccine. It is concluded that there are not enough data to verify or refute the hypothesis, and at the moment the use of BCG vaccine to prevent the spread of the infection even in high-risk groups would be unreasonable. В обзоре рассматривается недавно появившаяся гипотеза о том, что национальная политика BCG-вакцинации влияет на распространение COVID-19 в разных странах. Представлены сведения из 70 источников с эпидемиологическими показателями, свидетельствующие за и против данной гипотезы, с описанием возможных механизмов неспецифического противовирусного действия BCG-иммунизации. Сделан вывод, что для верификации или опровержения гипотезы пока недостаточно данных и в данный момент использование вакцины BCG для предотвращения распространения инфекции даже в группах высокого риска было бы необоснованно.

New coronaviral infection: Features of clinical course, capabilities of diagnostics, treatment and prevention in adults and children

First cases of new coronaviral infection were reported in Wuhan, Hubei Province, China in December 2019. The infection had caused the death of more than 100,000 people worldwide by the beginning of April 2020. This review analysed the characteristics of the infection course in adults and children, as well as capabilities of diagnostics, treatment and prevention of COVID-19. It is possible to allocate groups of high risk of development of severe forms of disease (elderly people, people with latent tuberculosis infection, adult patients with severe comorbidity) according to the published data. Currently there is limited epidemiological data on the prevalence, morbidity and mortality of COVID-19 in the child population. However, it is already possible to conclude that 90% of cases in children population have mild, moderate and asymptomatic course of the disease. Treatment of patients with COVID-19 is limited due to the lack of means for etiotropic therapy and the possibility of using of only symptomatic therapy. There are no vaccines for COVID-19 prevention.