Features of the Immune Response in COVID-19

BACKGROUND This review is devoted to the analysis of the features of the immune response in COVID-19. The review indicates the clinical manifestations of COVID-19, modern data on the immunopathogenesis of the disease and its complications are considered. AIM OF STUDY To clarify some pathogenetic mechanisms of the immune response in COVID-19, which can help in creating an algorithm for examining patients for early prognosis and prevention of severe course and complications of the disease. MATERIAL AND METHODS To achieve this goal, the results of domestic and foreign scientific studies on the pathogenesis, diagnosis and treatment of COVID-19 were analyzed. The literature search was carried out in electronic search engines Scopus and PubMed. For the analysis, scientific articles published in the period from 2019 to 2021 were selected;88% of analyzed works are not older than 5 years. CONCLUSION The late production of type I IFN, an increase in the level of pro-inflammatory monocytes, a decrease in the expression of HLA-DR on monocytes, violation of the presentation of the virus and the formation of specific lymphocytes, the death of T-lymphocytes and profound immunosuppression are of greatest importance for the development of a severe form of COVID-19. © 2023 Sklifosovsky Research Institute for Emergency Medicine. All rights reserved.

Impact of anti-epidemic measures on the dynamics of the incidence of COVID-19 in medical organizations with a psychoneurological profile

Aim of the study was to evaluate the impact of anti-epidemic measures (CAM) complex on the dynamics of the epidemic process of COVID-19 in a controlled cohort of patients. Material and methods. Patients from 30 social long-term care institutions of the city were included in the study, including neuropsychiatric boarding schools, boarding houses for labor veterans, gerontological centers, and houses for stage veterans. A total of 8303 patients participated in the study, of which 4237 were men (mean age 53.6 years) and 4066 were women (mean age 62.0 years). Vaccination was carried out with Gam-Covid-Vac. Results and discussion. For the entire observation period from March 2020 to August 2021, 1619, cases of COVID-19 or 19.5% of the total number of patients were registered among patients. At the initial epidemic stage (spring-summer 2020), the incidence of COVID-19 among patients was explosive. At the same time, in the autumn-winter period of 2020, an increase in the incidence of COVID-19 was also observed. However, much less pronounced than in April 2020. Despite the progress, it was decided to strengthen the sanitary and anti-epidemic regime in institutions with the introduction of additional preventive measures. One of the most effective long-term algorithms for reducing the infectious disease incidence was vaccination. In this regard, the Moscow Department of Healthcare suggested the need for voluntary vaccination of 100% of patients in all institutions at the beginning of 2021. In the spring of 2021, the number of cases began to increase in the city. The increase in the incidence of COVID-19 was insignificant among the patients of institutions: the maximum number of cases detected in one month during this period was 13 people (in April), or 60.5 times less than in April 2020, and 2.5 times less than in October 2020. The incidence of COVID-19 has become sporadic rather than epidemic. Conclusion. The introduction of CAM in long-term care social institutions in the early stages of the epidemic contributed to a decrease in the incidence of COVID 19. 100% vaccination of patients in combination with other prevention measures reduced the incidence of COVID-19 by more than 28 times. At the same time, it was found that there is a trend of increasing incidence depending on the increase in the level of independent activity of patients.Copyright © 2023 The authors.

Impact of anti-epidemic measures on the dynamics of the incidence of COVID-19 in medical organizations with a psychoneurological profile.

Aim of the study was to evaluate the impact of anti-epidemic measures (CAM) complex on the dynamics of the epidemic process of COVID-19 in a controlled cohort of patients. Material and methods. Patients from 30 social long-term care institutions of the city were included in the study, including neuropsychiatric boarding schools, boarding houses for labor veterans, gerontological centers, and houses for stage veterans. A total of 8303 patients participated in the study, of which 4237 were men (mean age 53.6 years) and 4066 were women (mean age 62.0 years). Vaccination was carried out with Gam-Covid-Vac. Results and discussion. For the entire observation period from March 2020 to August 2021, 1619, cases of COVID-19 or 19.5% of the total number of patients were registered among patients. At the initial epidemic stage (spring-summer 2020), the incidence of COVID-19 among patients was explosive. At the same time, in the autumn-winter period of 2020, an increase in the incidence of COVID-19 was also observed. However, much less pronounced than in April 2020. Despite the progress, it was decided to strengthen the sanitary and anti-epidemic regime in institutions with the introduction of additional preventive measures. One of the most effective long-term algorithms for reducing the infectious disease incidence was vaccination. In this regard, the Moscow Department of Healthcare suggested the need for voluntary vaccination of 100% of patients in all institutions at the beginning of 2021. In the spring of 2021, the number of cases began to increase in the city. The increase in the incidence of COVID-19 was insignificant among the patients of institutions: the maximum number of cases detected in one month during this period was 13 people (in April), or 60.5 times less than in April 2020, and 2.5 times less than in October 2020. The incidence of COVID-19 has become sporadic rather than epidemic. Conclusion. The introduction of CAM in long-term care social institutions in the early stages of the epidemic contributed to a decrease in the incidence of COVID 19. 100% vaccination of patients in combination with other prevention measures reduced the incidence of COVID-19 by more than 28 times. At the same time, it was found that there is a trend of increasing incidence depending on the increase in the level of independent activity of patients.Copyright © 2023 The authors.

The Rs17713054 and Rs1800629 Polymorphisms of Genes Lztfl1 and Tnfare Associated with Covid-19 Severity

Both genetic and non-genetic factors are responsible for high interindividual variability in response to SARS-CoV-2. Despite the fact that multiple genetic polymorphisms have been identified as risk factors of severe COVID-19, such polymorphisms are still insufficiently studied in the Russian population. The study was aimed to identify genetic determinants associated with severe COVID-19 in the sample of patients from the Russian Federation. The correlation of the rs17713054 polymorphism in gene LZTFL1 and rs1800629 polymorphism in gene TNF (tumor necrosis factor) with the COVID-19 severity was assessed. DNA samples obtained from 713 patients (324 males and 389 females) aged 18-95 with COVID-19 of varying severity were analyzed. The rs1800629 polymorphism of gene TNF (OR = 1.5;p = 0.02) and rs17713054 polymorphism of gene LZTFL1 (OR = 1.60;p = 0.0043) were identified as risk factors of severe disease. The TNF polymorphism rs1800629 and LZTFL1 polymorphism rs17713054 could be considered as potential predictive biomarkers. The rs17713054 G > A polymorphism was strongly associated with severe disease. In the future the findings may provide the basis for the development of test-systems for prediction of the risk of severe viral respiratory diseases.

Anti-Interferon Alpha Autoantibodies and Their Significance in Covid-19

During the last two years, treatment of patients with novel coronavirus infection COVID-19 remains an urgent health problem. Interferon proteins are known to play a significant role in antiviral immunity. Some pathological conditions are accompanied by production of neutralizing autologous immunoglobulins against own host interferons (autoIFN-Abs). There is evidence that autoantibodies against interferons alpha and omega are detected in patients with life-threatening course of COVID-19 pneumonia. The aim of our study was to analyze prevalence of autoantibodies against interferon alpha in patients with COVID-19 coronavirus infection and assess their impact on clinical course of the disease. We examined 70 patients with severe COVID-19, who received inpatient treatment at the intensive care units. Serum autoantibodies against interferon alpha were determined on day 8-50 after disease onset by using solid-phase enzyme immunoassay ( ELISA). Patients were divided into 2 groups: those with and without (group 2) autoantibodies against interferon alpha (group 1). Anti-COVID serum from 57 donors was used a control. Among patients, autoantibodies against interferon alpha were detected in 13 (18%) subjects, which level ranged from 26.8 to 1000 ng/ml. Among donors, autoIFN-Abs were detected in 5 (8.8%) subjects at trace concentrations (from 1.65 to 12.0 ng/ml). Respiratory failure developed significantly more often in patients with auto-IFN-Abs. While analyzing laboratory parameters, it was noted that the concentration of C-reactive protein was significantly higher in the group of patients with auto-IFN-Abs. Mortality rate of patients with high auto-IFN-Abs levels was 60%. In conclusion, it was found that serum autoantibodies against IFN alpha in COVID-19 patients caused lung damage that significantly more often required hardware respiratory support, so comparable by duration with it for patients without auto-IFN-Abs. High concentrations of auto-IFN-Abs (more than 100 ng/ml) in patients with COVID-19 can be considered as a predictor of unfavorable disease outcome.

Regulation of lymphocyte apoptosis in intensive care patients with COVID-19

Severity of a new coronavirus infection (COVID-19) caused by the SARS-COV-2 virus is largely due to abnormal immune condi-tion in these patients. Lymphopenia is observed in 85% of patients with severe COVID-19 that may be associated with enhanced apoptosis of lymphocytes. Objective. To analyze apoptotic death of lymphocytes and changes in proteins regulating apoptosis in patients with severe COVID-19. Material and methods. We analyzed 93 ICU patients. All patients were divided into three groups depending on severity and outcomes of disease: group 1 consisted of 53 patients with favorable course and outcomes of disease, group 2 included 26 patients with unfavorable course and favorable outcomes of disease, group 3 included 14 patients with unfavorable course and outcomes of disease. Blood sampling for analysis of apoptosis markers was carried out in 5-12 and 14-18 days after clinical manifestation of disease. Quantitative parameters of lymphocyte apoptosis were evaluated using flow cytometry. Regulatory proteins of apop-tosis (phosphorylated AKT, JNK, BAD, BCL-2, p-53, active caspase 8 and 9) were determined on the Luminex platform. We also assessed concentration of leukocytes, relative and absolute lymphocyte count, concentration of C-reactive protein (CRP), procal-citonin and lactate dehydrogenase. Results. Study groups significantly differed in NEWS score (p=0.001), SOFA score (p=0.001), CRP level (p=0.001), severity of lymph-openia (p=0.001) and level of CD14+HLA-DR+ monocytes (p=0.001). Quantitative parameters of lymphocyte apoptosis did not cor-relate with lymphopenia. The highest rates of lymphocyte apoptosis were observed in patients with favorable course and outcomes of disease. There was no correlation between concentration of lymphocytes in venous blood and level of proteins regulating apoptosis. Conclusion. Patients with severe COVID-19 are characterized by abnormal induction of lymphocyte apoptosis through external and internal activation pathways in response to viral aggression. In deceased patients, pro-apoptotic factors prevailed while activity of anti-apoptotic factors was decreased. © 2023, Media Sphera Publishing Group. All rights reserved.

THE RS17713054 AND RS1800629 POLYMORPHISMS OF GENES LZTFL1 AND TNF ARE ASSOCIATED WITH COVID-19 SEVERITY

Both genetic and non-genetic factors are responsible for high interindividual variability in response to SARS-CoV-2. Despite the fact that multiple genetic polymorphisms have been identified as risk factors of severe COVID-19, such polymorphisms are still insufficiently studied in the Russian population. The study was aimed to identify genetic determinants associated with severe COVID-19 in the sample of patients from the Russian Federation. The correlation of the rs17713054 polymorphism in gene LZTFL1 and rs1800629 polymorphism in gene TNF (tumor necrosis factor) with the COVID-19 severity was assessed. DNA samples obtained from 713 patients (324 males and 389 females) aged 18-95 with COVID-19 of varying severity were analyzed. The rs1800629 polymorphism of gene TNF (OR = 1.5;p = 0.02) and rs17713054 polymorphism of gene LZTFL1 (OR = 1.60;p = 0.0043) were identified as risk factors of severe disease. The TNF polymorphism rs1800629 and LZTFL1 polymorphism rs17713054 could be considered as potential predictive biomarkers. The rs17713054 G > A polymorphism was strongly associated with severe disease. In the future the findings may provide the basis for the development of test-systems for prediction of the risk of severe viral respiratory diseases.

Effect of vitamin D (25-OH D3 ) concentration on the course and outcomes of COVID-19 in intensive care patients

Objective. To study the effect of vitamin D concentration on the course and outcomes of COVID-19 in intensive care patients. Material and methods. A prospective study included 43 ICU patients admitted to the Sklifosovsky Research Institute for Emergency Care with a confirmed diagnosis of a novel coronavirus infection. Single blood sampling was performed in 1—2 days after admission for analysis of 25-OH D3 concentration. Patients were divided into 2 groups with normal and reduced level of vitamin D. We analyzed chest CT data and laboratory parameters at admission and at the peak of cytokine storm. Administration of IL-6 antagonists and IL-6 receptor blockers was compared. We also compared the need for respiratory support, period between the onset of disease and respiratory therapy, its total duration and type of respiratory support, incidence of complications (sepsis, multiple organ failure, nosocomial pneumonia, acute kidney injury, thrombosis and hemorrhagic events). We analyzed the outcomes of disease, length of ICU-stay and hospital-stay. Results. Patients with normal vitamin D level at admission were characterized by lower serum C-reactive protein (15.41±7.96 vs. 63.271±11.988;p=0.029), while lymphocyte count (1.69±0.49 vs. 0.921±0.0719;p=0.029), leukocyte count (7.88±1.33 vs. 5.305±0.468;p=0.041) and serum lactate dehydrogenase (454.50±102.5 vs. 271.315±16.867;p=0.024) were higher. Minimum daily saturation at the peak of cytokine storm was higher in patients with normal vitamin D level (95.2±1.39 vs. 90.947±0.9585;p=0.044). Conclusion. Patients with vitamin D deficiency have a more pronounced inflammatory response in initial stages of disease and more severe lung damage at the stage of cytokine storm. However, this does not increase aggressiveness and duration of respiratory support, ICU-and hospital-stay. There was no worsening of the outcomes too. © S.S. PETRIKOV1, G.E. SAVKOV1, M.A. GODKOV1, N.V. BOROVKOVA1, A.M. KVASNIKOV1, D.A. LEBEDEV1, K.V. KISELEV2, K.A. POPUGAEV1.

ANTI-INTERFERON ALPHA AUTOANTIBODIES AND THEIR SIGNIFICANCE IN COVID-19

During the last two years, treatment of patients with novel coronavirus infection COVID-19 remains an urgent health problem. Interferon proteins are known to play a significant role in antiviral immunity. Some pathological conditions are accompanied by production of neutralizing autologous immunoglobulins against own host interferons (auto-IFN-Abs). There is evidence that autoantibodies against interferons alpha and omega are detected in patients with life-threatening course of COVID-19 pneumonia. The aim of our study was to analyze prevalence of autoantibodies against interferon alpha in patients with COVID-19 coronavirus infection and assess their impact on clinical course of the disease. We examined 70 patients with severe COVID-19, who received inpatient treatment at the intensive care units. Serum autoantibodies against interferon alpha were determined on day 8–50 after disease onset by using solid-phase enzyme immunoassay (ELISA). Patients were divided into 2 groups: those with and without (group 2) autoantibodies against interferon alpha (group 1). Anti-COVID serum from 57 donors was used a control. Among patients, autoantibodies against interferon alpha were detected in 13 (18%) subjects, which level ranged from 26.8 to 1000 ng/ml. Among donors, auto-IFN-Abs were detected in 5 (8.8%) subjects at trace concentrations (from 1.65 to 12.0 ng/ml). Respiratory failure developed significantly more often in patients with auto-IFN-Abs. While analyzing laboratory parameters, it was noted that the concentration of C-reactive protein was significantly higher in the group of patients with auto-IFN-Abs. Mortality rate of patients with high auto-IFN-Abs levels was 60%. In conclusion, it was found that serum autoantibodies against IFN alpha in COVID-19 patients caused lung damage that significantly more often required hardware respiratory support, so comparable by duration with it for patients without auto-IFN-Abs. High concentrations of auto-IFN-Abs (more than 100 ng/ml) in patients with COVID-19 can be considered as a predictor of unfavorable disease outcome.

Results of RT-PCR test for the presence of SARS-CoV-2 in multiple organs of post-COVID patients who died from causes other than COVID-19

The aim of this research work was to study the ability of SARS-CoV-2 to persist in multiple organs of people who have recovered from COVID-19. For this purpose, autopsy material was used from patients with a history of COVID-19 who died from causes unrelated to a new coronavirus infection. Autopsy material collected from 11 different organs was analyzed for the presence of SARS-CoV-2 RNA using real-time polymerase chain reaction (RT-PCR). Among the organs tested, SARS-CoV-2 RNA persisted longest in the bronchi and lungs. Thus, in both patients tested positive more than 100 days after recovery, SARS-CoV-2 RNA was detected only in the bronchi and lungs. On the contrary, the shorter the recovery time was, the more organs were found to have SARS-Cov-2 RNA. SARS-CoV-2 RNA was most frequently detected in biomaterials of deceased people over 80 years of age, which may indicate a longer period of virus elimination in the elderly. No correlation between the distribution of SARS-CoV-2 across organs and the age of patients could be detected, but it was shown that SARS-CoV-2 persisted in more organs in males after recovery. In females, SARS-CoV-2 RNA was found predominantly in the bronchi and lungs.

Formation of Herd Immunity to SARS-CoV-2 in the Population of Moscow

Relevance. The research of the dynamics of population immunity formation is an important component of epidemiological surveillance, especially during the pandemic period. Identifying the features of the course of the epidemic process of a particular infection provides an opportunity to make the right decisions both in the fight against the disease and in its prevention. Aims. Evaluate the dynamics of the formation of collective immunity in the population of the city of Moscow. Materials & Methods. The presence of immunity in the population was assessed by immunochemiluminescent analysis of blood serum of patients for the presence of antibodies IgM and IgG to SARS-CoV-2. Results. During the analysis of the annual dynamics of IgM detection, a gradual decrease in this indicator was recorded. The dynamics of the combined detectability of IgM/IgG has a wave-like course. It should be noted that the curves of the dynamics of the IgM detectability and the combined IgM/IgG detectability reflect multidirectional trends: the summer rise in the IgM detectability coincides with the fall and the lowest values of the IgM/IgG detectability indicator. Afterwards, the decrease in the IgM detectability is accompanied by an increase in the combined IgM / IgG detectability. Detectability of IgG has a pronounced tendency to rise with short time intervals of decline. In the first three months of testing, a gradual decrease in detectability was recorded from 15.2 to 10.8%. However, since August, there has been a new increase in detectability of IgG to 45.5% in marth and subsequent stabilization in the range of 44.3–45.5%. Conclusions. The level of seroprevalence for the period of May 2021 is 44.3%. Detection during screening of patients with IgM and partially with a combination of IgM / IgG may indicate the presence of a significant hidden component of the epidemic process, which may lead to an increase in morbidity. © Godkov MA, et al.