Дефекты в системе интерферонов, ассоциированные с дефицитом естественных киллерных клеток и Т-лимфоцитов у пациентов с COVID-19

BackgroundBiologic treatments are inherently associated with an increased risk of infections, and recipients are intuitively considered at-risk for a more severe course of COVID-19. However, the actual risks are not fully described, neither are the appropriate adjustments needed to mitigate such risks. MethodsNation-wide registry was set up by Israeli IBD Section, to characterize course of COVID-19 in IBD patients who contacted SARS-CoV-2 infection while on biologics. We prospectively collected demographic and clinical data, and analyzed COVID-19 outcomes with regard to the specific treatments.ResultsBetween Apr and Oct 2020, 144 patients with an established IBD diagnosis and confirmed COVID-19 were enrolled at 20 IBD referral centers. The majority of patients was under the age of 40 (113, 78%), 9 (6%) were younger than 18, only 4 patients (3%) over the age of 70.94 patients received biologics, as monotherapy (76, 52.8%), combined with immunomodulators (9, 10%) or concomitant corticosteroids (9, 10%).37 patients (26%) were reported with moderate and severe COVID-19 course, third of them (13) on biologics. 24 patents (17%) were admitted for hospitalization, the rest managed in home setting (114, 79%) and hotels converted into makeshift healthcare facilities (6, 4%). Fifteen patients (10%) required non-invasive ventilation and oxygen support, 3 patients (2%) went on mechanical ventilation. All patients recovered uneventfully, with no mortalities reported.Age was the most significant factor associated with moderate and severe disease. We found no correlation between bowel disease activity and the severity of COVID-19 course.The rate of serious COVID-19 for the 94 patients who had received biologics was significantly lower than that of 50 patients who were not treated with biologics (13/94 vs 24/50; RR 0.29 [95% CI, 0.161–0.515]; p < 0.0001). On adjusting for age, gender, comorbidities, IBD phenotype and activity, the surprising ameliorating effect associated with biologics was profound and significant (OR, 0.082 [95% CI 0.009-0.621], p =0.013) in all age categories. ConclusionOur results are reassuring and encouraging, and do not suggest that therapeutic immune suppression renders IBD patients particularly vulnerable for more severe course of the COVID-19. Adjusted odds for severe COVID-19 course actually decreased significantly in patients treated with biologics. It could be speculated that cytokine inhibition may mitigate progression of the infection to a devastating hyperinflammatory state. Continuing necessary maintenance immune suppression seems to be appropriate and safe approach, despite the COVID-19 pandemic.

Objective: evaluation of the clinical and economic efficiency of using Levilimab in the treatment of moderate and severe COVID-19 based on real world data (RWD).Material and methods. A single-center observational retrospective case-control study was performed. According to the matching algorithm, 834 pairs of patients with moderate and 347 pairs with severe infection were selected, similar in gender, age, vaccination status, severity of the disease and the level of C-reactive protein.Results. The clinical efficiency of Levilimab with respect to in-hospital mortality was demonstrated both for the moderate course (6% in the Levilimab group and 10% in the standard therapy group; odds ratio (OR) 1.71; 95% confidence interval (CI) 1.19–2.47; p&lt;0.01) and for the severe course of COVID-19 (63% and 82%, respectively; OR 2.70; 95% CI 1.90–3.82; p&lt;0.01). The costs per 1 treated patient were also higher in the Levilimab therapy groups: the difference in costs compared to the standard therapy group for patients with moderate disease was 54 665.30 rubles, with severe disease – 91 285.85 rubles. The estimated cost of the additional effectiveness of Levilimab for the moderate course of the disease was 13,666.32 rubles, for the severe course – 4,804.51 rubles.Conclusion. The use of Levilimab for the treatment of moderate and severe COVID-19 is feasible both from a clinical and economic points of view. Conducting RWD trials is an important tool to understand the effectiveness of medical technologies in real clinical practice.

The long-term course of protection against severe COVID-19 courses by vaccine-induced or hybrid immunity in Germany is unclear. We studied 146 457 cases aged 60-99 years in the German federal state of Bavaria who were immunized against COVID-19 and tested positive for it from February 2022 to January 2023. We calculated adjusted hazard ratios for a severe course (hospitalization or death due to COVID-19) for different intervals between the onset of full primary or booster immunity and the date of the infection. 3342 (2.3%) severe courses of COVID-19 were observed in the first 60 days after the infection. The risk of a severe course rose with the interval between the onset of immune protection and the infection (adjusted hazard ratios and 95% confidence intervals at 6, 9, 12, and 15 months: 1.14 [1.08; 1.20]; 1.33 [1.24; 1.42]; 1.39 [1.25; 1.54]; 1.61 [1.35; 1.93]). The risk rose more slowly when mRNA-based vaccines were used exclusively. In a previous study, we observed 82% initial efficacy in cases aged 60 and above who received a booster vaccination (compared to unvaccinated cases) and an absolute risk reduction of 2.1%. If one extrapolates these findings to the current study, the residual efficacy and absolute risk reduction are found to be approximately 71% and 1.8% (respectively) at 6 months, and 32% and 0.8% at 15 months. These results indicate that, during the Omicron wave, the protection of older persons against a severe COVID-19 course gradually declined from six months after vaccination onward. The limitations of this study include confounders that could not be taken into account, possible misclassification of the cause of death, and selection bias due to missing information about vaccination status and severe COVID-19 courses.

BackgroundOlder individuals tend to include less physical activity in their routine and are more prone to chronic diseases and severe medical complications, making them the most burdened group that is losing years of life due to pandemic-related premature mortality.This research aimed to assess the lifestyle factors that affect the COVID-19 course among patients ≥ 65 years old. MethodsThe study included 568 convalescents (64.1% women and 35.9% men) with persistent clinical symptoms after isolation. The mean age was 70.41 ± 4.64 years (minimum: 65 years; maximum: 89 years). The patients completed the questionnaire during their in-person visit to the medical center. The survey included questions regarding their health status when suffering from COVID-19, basic sociodemographic data, and medical history concerning chronic conditions and lifestyle. ResultsPhysical inactivity (p < 0.001) and feeling nervous (p = 0.026) increased the risk of having a severe disease course. Coronary artery disease raised both the risk of a severe disease course (p = 0.002) and the number of present symptoms up to 4 weeks (p = 0.039). Sleep disturbances increased the number of symptoms during infection (p = 0.001). The occurrence of any symptoms was also associated with the female sex (p = 0.004). The severity of the course was associated with longer persistent symptoms (p < 0.001) and a greater number of symptoms (p = 0.004); those with a more severe course were also at a greater risk of persistent symptoms for up to 4 weeks (p = 0.006). Senior citizens in the third pandemic wave suffered with more severe disease (p = 0.004), while illness during the fourth (p = 0.001) and fifth (p < 0.001) waves was associated with a lower risk of persistent symptoms for up to 4 weeks. The disease duration was significantly shorter among vaccinated patients (p = 0.042). ConclusionsElderly COVID-19 patients should re-think their lifestyle habits to consider a physical activity level that is adjusted to their abilities, in order to decrease the risk of a severe disease course and to further limit both the number and duration of symptoms.The research was carried out in accordance with the Declaration of Helsinki, and approval from the Bioethics Committee of Lodz Regional Medical Chamber to conduct the study was obtained (approval number 0115/2021). The PoLoCOV-Study ClinicalTrials.gov identifier is NCT05018052.

Актуальность: Коронавирусная инфекция — болезнь, вызывающая дыхательную недостаточность и осложнения у определенных групп людей, приводящие к смерти. Факторы, ассоциированные с тяжелым течением COVID-19, к текущему моменту достаточно хорошо изучены, в связи с чем, на современном этапе необходим их поиск и изучение в отдельных группах лиц, отличающихся по возрасту, полу, этнической принадлежности, наличию фоновых заболеваний и т.д. для разработки более персонализированных подходов к профилактике тяжелого течения. Цель исследования: провести сравнительный анализ факторов, ассоциированных с тяжелым течением COVID-19 у лиц до 60 лет и старше 60 лет и оценить их прогностическую значимость при комбинации факторов. Материалы и методы исследования: был проведен ретроспективный анализ клинических и лабораторных показателей 812 больных. Для идентификации факторов, ассоциированных с развитием тяжелого течения COVID-19, использовался множественный логистический регрессионный анализ. Для оценки прогностической значимости совокупности выявленных статистически значимых факторов в развитии тяжелого течения COVID-19 был проведен ROC-анализ. Результаты исследования: Многофакторный логистический регресионный анализ показал, что у больных до 60 лет диагноз сахарного диабета в анамнезе (OR=2,561, р=0,048), лимфопения (OR=2,133, p=0,030), наличие пневмонии при поступлении (OR=2,556, p=0,011), учащенное дыхание (OR=3,497, p=0,001), низкая сатурация (OR=4,076, p=0,006) были достоверно связаны с развитием тяжелого течения COVID-19. У больных старше 60 лет наличие сахарного диабета (OR=1,899, р=0,029), учащенное дыхание (OR=2,338, p=0,007) и низкая сатурация (OR = 4,248, p &lt;0,0001) были достоверно связаны с развитием тяжелого течения COVID-19. В группах до 60 лет и старше 60 лет прогностическое значение комбинации всех соответствующих группам статистически значимых факторов было равно среднему уровню (AUC=0,760 и AUC=0,709 соответственно). Заключение: Факторы, ассоциированные с развитием тяжелого течения COVID-19, у лиц пожилого и среднего возраста имеют некоторые отличия, связанные с особенностями патогенеза заболевания. Для лиц до 60 лет факторами, ассоциированными с тяжелым течением COVID-19, являются сахарный диабет, наличие пневмонии при поступлении, одышка, низкая сатурация и лимфопения. Для лиц старше 60 лет факторами, ассоциированными с тяжелым течением COVID-19, являются наличие сахарного диабета, одышка и низкая сатурация. Совокупность всех изученных факторов значительно повышает риск формирования тяжелого течения COVID-19 в обеих возрастных группах. Introduction: Coronavirus infection is a disease that causes respiratory failure and complications in certain groups of people, leading to death. The factors associated with the severe course of COVID-19 have been fairly well studied by now; at the present stage, it is necessary to search for and study them in separate groups of people that differ in age, gender, ethnicity, the presence of background diseases, etc. to develop more personalized approaches to severe disease prevention. Objective: To conduct a comparative analysis of the factors associated with the severe course of COVID-19 in people under and over 60 years of age and evaluate their prognostic significance in combination of factors. Materials and methods: A retrospective analysis of the clinical and laboratory parameters of 812 COVID-19 patients was carried out. Multiple logistic regression analysis was used to identify factors associated with the development of severe COVID-19. ROC analysis was performed to assess the prognostic significance of the set of identified statistically significant factors in the development of a severe course of COVID-19. Results: Multivariate logistic regression analysis showed that patients under 60 diabetes mellitus (OR=2,561, p=0,048), lymphopenia (OR=2,133, p=0,030), and pneumonia at admission (OR=2,556, p=0,011), rapid breathing (OR=3,497, p=0,001), low saturation (OR=4,076, p=0,006) were significantly associated with the development of severe COVID-19. At the same time, in patients older than 60 years, the presence of diabetes mellitus (OR=1,899, p=0,029), rapid breathing (OR=2,338, p=0,007) and low saturation (OR=4,248, p&lt;0,0001) were significantly associated with the development of a severe course of COVID-19. In groups under 60 and over 60 years of age, the prognostic value of the combination of all statistically significant factors corresponding to the groups was equal to the average level (AUC=0,760 and AUC=0,709, respectively) Conclusion: Factors associated with the development of a severe course of COVID-19 in elderly and middle-aged people have some differences related to the pathogenesis of the disease. For individuals under 60 years of age, factors associated with severe COVID-19 are diabetes mellitus, the presence of pneumonia on admission, dyspnea, low oxygen saturation, and lymphopenia. For individuals over 60 years of age, factors associated with severe COVID-19 are the presence of diabetes mellitus, shortness of breath, and low saturation. The combination of all the studied factors significantly increases the risk of developing a severe course of COVID-19 in both age groups. Кіріспе: Коронавирустық инфекция - бұл адамдардың белгілі бір топтарында тыныс алу жеткіліксіздігі мен асқынуларды тудыратын, өлімге әкелетін ауру. Қазіргі уақыттаCOVID-19 ауыр ағымына байланысты факторлар жеткілікті түрде зерттелді, осы кезеңде оларды жасы, жынысы, этникалық құрамы, фондық аурулар бойынша ерекшеленетін адамдардың жекелеген топтарында іздеу және зерттеу аурудың ауыр ағымының алдын алудағы жекелендірілген тәсілдерін әзірлеуге қажет. Зерттеу мақсаты: 60 жасқа дейінгі және 60 жастан асқан адамдардаCOVID-19 ауыр ағымымен байланысты факторларға салыстырмалы талдау жүргізу және факторлардың жиынтығымен олардың болжамдық маңыздылығын бағалау. Зерттеудің материалдары мен әдістері: 812 науқастың клиникалық және зертханалық көрсеткіштеріне ретроспективті талдау жасалды. Ауыр COVID-19 дамуына байланысты факторларды анықтау үшін бірнеше логистикалық регрессиялық талдау қолданылды. COVID-19 ауыр ағымының дамуындағы анықталған статистикалық маңызды факторлар жиынтығының болжамдық маңыздылығын бағалау үшінROC талдауы жүргізілді. Зерттеу нәтижелері: Көп нұсқалы логистикалық регрессиялық талдау60 жасқа дейінгі пациенттерде қант диабеті(OR=2,561, p=0,048), лимфопения (OR=2,133, p=0,030) және қабылдау кезінде пневмония (OR=2,556, p=0,011) болғанын көрсетті. жылдам тыныс алу(OR=3,497, p=0,001), төмен қанықтылық (OR=4,076, p=0,006) ауыр COVID-19 дамуымен айтарлықтай байланысты болды. 60 жастан асқан емделушілерде қант диабетінің болуы (OR=1,899, p=0,029), жылдам тыныс алу(OR=2,338, p=0,007) және қанығу деңгейінің төмендігі(OR=4,248, p&lt;0,0001) айтарлықтай дәрежеде байланысты болды. COVID-19 ауыр ағымының дамуы. 60 жастан кіші және60 жастан асқан топтарда топтарға сәйкес келетін барлық статистикалық маңызды факторлардың комбинациясының болжамдық мәні орташа деңгейге тең болды (тиісіншеAUC=0,760 және AUC=0,709). Қорытынды: Егде және орта жастағы адамдарда COVID-19 ауыр ағымының дамуына байланысты факторлар аурудың патогенезіне байланысты кейбір айырмашылықтарға ие. 60 жасқа толмаған адамдар үшін ауыр COVID-19-мен байланысты факторлар қант диабеті, қабылдау кезінде пневмонияның болуы, ентігу, оттегімен қанығудың төмендігі және лимфопения болып табылады. 60 жастан асқан адамдар үшін ауырCOVID-19-мен байланысты факторлар қант диабетінің болуы, ентігу және қанықтылықтың төмендігі болып табылады. Барлық зерттелген факторлардың қосындысы екі жас тобында да COVID-19 ауыр ағымының даму қаупін айтарлықтай арттырады.

Infection with SARS-CoV-2 results in mild to severe COVID-19 disease courses. Several studies showed the association of impaired T-cell responses and certain HLA haplotypes with disease severity. However, it remained unclear if T-cell activation was compromised due to a general reduction of presented epitopes or other intrinsic factors within APCs or T cells. Furthermore, a potential reduction of presented epitopes would suggest if an upcoming SARS-CoV-2 variant could escape T-cell immunity. Hence, knowledge about the T-cell epitope landscape of SARS-CoV-2 would allow to better understand mechanisms leading to severe disease and to estimate the potential stability of the T-cell response in light of virus evolution, which might provide insights for future vaccine designs. Hence, in the present study, the T-cell epitope landscape of SARS-CoV-2 was determined via in vitro T-cell stimulation plus in silico prediction. HLAs associated with mild and severe disease courses showed almost the same potential in epitope presentation, suggesting intrinsic factors of APCs or T cells as contributors to the more severe disease courses. As T-cell epitopes did also not originate from regions of SARS-CoV-2 having shown high mutation rates in the past, a relatively stable T-cell response can be expected regarding new SARS-CoV-2 strains in the future. Analysis of the T-cell epitope landscape of SARS-CoV-2 suggests T-cell intrinsic factors as likely modulators of disease severity and that the capacity of MHC-peptide presentation remains stable among circulating SARS-CoV-2 viral strains.

Risk of Severe Sars-Cov-2 Infections in COVID-19 Vaccinated Individuals with Hematologic Malignancies (SAVE HEM): A Nationwide Cohort Study in the Netherlands

Dexamethasone and remdesivir: finding method in the COVID-19 madness

BACKGROUND: The new coronavirus infection (COVID-19) gained the pandemic status in 2020, and despite the fact that since then the virus has become less pathogenic, its virulence has increased by 2023. Well-vascularized organs and tissues, including the retina, represent the target for coronavirus. The etiopathogenesis of COVID-associated retinopathy, first described in 2021, still remains poorly understood, and its forms and occurrence frequency during different periods of the infectious process vary greatly. AIM: To identify the main characteristics of the COVID-associated retinopathy in patients with moderate and severe COVID-19 course during the acute period of the disease. MATERIALS AND METHODS: The study, conducted in 2021 (group 1) and 2023 (group 2), included patients with confirmed COVID-19 of moderate to severe course during the first 7 days from the onset of symptoms. Group 1 included 46 people, mean age 65.5 years, and group 2 included 55 people, mean age 69.3 years. The ophthalmologic examination was carried out in the “red zone” and intensive care unit, and included examination of the anterior segment of the eye, indirect ophthalmoscopy, and fundus photography using a portable hand-held digital fundus camera (Smartscope M5, Optomed, Finland). Hypertension, diabetes mellitus, volume of lung damage, invasive mechanical ventilation, and anticoagulant therapy were considered as conditions affecting retinal microcirculation. RESULTS: The observation groups were homogeneous in terms of gender, age, and concomitant diseases. The incidence of ophthalmoscopic findings in group 1 was 17.3%, and in group 2 — 12.7%. Most often, during the first 7 days of the disease, signs of angiopathy were observed: dilatation of blood vessels, irregularity of their diameter and tortuosity. Among focal changes, there were multiple retinal hemorrhages (6.5% and 3.6%) and cotton wool spots (4.3% and 5.4%). In patients with fundus changes, diabetes mellitus was significantly less common (in group 1, 25% vs. 39%, p 0.001; in group 2, 28% vs. 44%, p 0.001), as well as arterial hypertension (in group 1, 55% vs. 66%, p = 0.003; in group 2 28% vs. 83%, p 0.001). In group 1, there was a higher proportion of patients treated in intensive care unit, as in group 2 (37% vs. 17%, p 0.001), but in group 2, patients with identified retinal changes were more likely to receive therapeutic doses of anticoagulants (33% vs. 12%, p 0.001). CONCLUSION: The main characteristics of COVID-associated retinopathy in patients with moderate to severe COVID-19 during the acute period of the disease are dilatation and pathological tortuosity of the retinal arteries and veins, intraretinal hemorrhages and cotton wool spots. The connection between COVID-associated retinopathy and concomitant to the infectious process cardiovascular conditions has not been established. Retinopathy associated with coronavirus infection, with absolute similarity of clinical manifestations, was significantly more common in 2021 than in 2023.

BackgroundValidated clinical prediction models to identify children with poor prognosis at the time of juvenile idiopathic arthritis (JIA) diagnosis would be very helpful for tailoring treatments, and avoiding under- or over-treatment. Our objective was to externally validate Nordic clinical prediction models in Canadian patients with JIA.MethodsWe used data from 513 subjects at the 3-year follow-up from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort. The predicted outcomes were non-achievement of remission, severe disease course, and functional disability. The Nordic models were evaluated exactly as published and after fine-tuning the logistic regression coefficients using multiple data splits of the Canadian cohort. Missing data was handled with multiple imputation, and prediction ability was assessed with C-indices. C-index values > 0.7 were deemed to reflect helpful prediction.ResultsOverall, 81% of evaluable patients did not achieve remission off medications, 15% experienced a severe disease course, and 38% reported disability (CHAQ score > 0). The Nordic model for predicting non-achievement of remission had a C-index of 0.68 (95% CI 0.62–0.74), and 0.74 (0.67–0.80) after fine-tuning. For prediction of severe disease course, it had a C-index of 0.69 (0.61–0.78), and 0.79 (0.68–0.91) after fine-tuning. The fine-tuned Nordic model identified 85% of the cohort as low risk for a severe disease course (< 20% chance) and 7% as high risk (> 60% chance). The Nordic model to predict functional disability had a C-index of 0.57 (0.50–0.63), and 0.51 (0.39–0.63) after fine-tuning.ConclusionsFine-tuned Nordic models, combining active joint count, physician global assessment of disease activity, morning stiffness, and ankle involvement, predicted well non-achievement of remission and severe disease course in Canadian patients with JIA. The Nordic model for predicting disability could not predict functional disability in Canadian patients.

Background Crohn’s disease (CD) is characterized by a heterogeneous disease course and treatment response. There is a clinical need to identify CD patients at diagnosis who are at risk for developing a severe disease course. Patient stratification using state-of-the-art clinical, serological or genetic markers does not predict disease course sufficiently to facilitate clinical decision making. The current study aimed to investigate the additive predictive value of histopathological features at diagnosis to discriminate between patients with a long-term mild and severe disease course. Methods Diagnostic biopsies from treatment-naïve CD patients with mild or severe disease courses in the first 10 years after diagnosis (i.e. based on the number of quarterly flares) were reviewed by two senior gastrointestinal pathologists after developing a standardized form comprising 15 histopathological features related to acute and chronic inflammation. Multivariable logistic regression models were built to identify predictive features and compute receiver operating characteristics (ROC) curves. Model 1 included clinically relevant baseline characteristics (Montreal classification, smoking status and gender). Next, histopathological were added by applying two different model-building strategies (forward selection and purposeful selection algorithm)(Model 2). Prediction models were internally validated using bootstrapping to obtain optimism-corrected performance estimates. Results In total, 817 biopsies from 137 CD patients (64 mild disease course, 73 severe disease course) were included. Based on clinical baseline characteristics alone, disease course could only be moderately predicted (Model 1 Area under ROC (AUROC): 0.738 (optimism 0.018), 95%CI 0.65–0.83, sensitivity 83.6%, specificity 53.1%). When adding histopathological features, in colonic, but not ileal, biopsies a combination of (1) basal plasmacytosis, (2) severe lymphocyte and plasma cell infiltration in the lamina propria, (3) Paneth cell metaplasia and (4) absence of ulcers were identified and resulted in significantly better prediction of a severe disease course (Model 2 AUROC: 0.883 (optimism 0.033), 95%CI 0.82–0.94, sensitivity 80.4%, specificity 84.2%, model 2 vs. model 1 AUROC p = 0.001)[Figure 1]. Conclusion In this first study investigating the additive predictive value of multiple histopathological features in biopsies at CD diagnosis, we found that certain features of chronic inflammation in colonic biopsies contributed to prediction of a severe disease course, thereby presenting a novel approach to improve stratification and facilitate clinical decision making.

BackgroundInfection by the SARS-Cov-2 virus produces in humans a disease of highly variable and unpredictable severity. The presence of frequent genetic single nucleotide polymorphisms (SNPs) in the population might lead to a greater susceptibility to infection or an exaggerated inflammatory response. SARS-CoV-2 requires the presence of the ACE2 protein to enter in the cell and ACE2 is a regulator of the renin-angiotensin system. Accordingly, we studied the associations between 8 SNPs from AGTR1, ACE2 and ACE genes and the severity of the disease produced by the SARS-Cov-2 virus.Methods318 (aged 59.6±17.3 years, males 62.6%) COVID-19 patients were grouped based on the severity of symptoms: Outpatients (n = 104, 32.7%), hospitalized on the wards (n = 73, 23.0%), Intensive Care Unit (ICU) (n = 84, 26.4%) and deceased (n = 57, 17.9%). Comorbidity data (diabetes, hypertension, obesity, lung disease and cancer) were collected for adjustment. Genotype distribution of 8 selected SNPs among the severity groups was analyzed.ResultsFour SNPs in ACE2 were associated with the severity of disease. While rs2074192 andrs1978124showed a protector effectassuming an overdominant model of inheritance (G/A vs. GG-AA, OR = 0.32, 95%CI = 0.12–0.82; p = 0.016 and A/G vs. AA-GG, OR = 0.37, 95%CI: 0.14–0.96; p = 0.038, respectively); the SNPs rs2106809 and rs2285666were associated with an increased risk of being hospitalized and a severity course of the disease with recessive models of inheritance (C/C vs. T/C-T/T, OR = 11.41, 95% CI: 1.12–115.91; p = 0.012) and (A/A vs. GG-G/A, OR = 12.61, 95% CI: 1.26–125.87; p = 0.0081). As expected, an older age (OR = 1.47), male gender (OR = 1.98) and comorbidities (OR = 2.52) increased the risk of being admitted to ICU or death vs more benign outpatient course. Multivariable analysis demonstrated the role of the certain genotypes (ACE2) with the severity of COVID-19 (OR: 0.31, OR 0.37 for rs2074192 and rs1978124, and OR = 2.67, OR = 2.70 for rs2106809 and rs2285666, respectively). Hardy-Weinberg equilibrium in hospitalized group for I/D SNP in ACE was not showed (p<0.05), which might be due to the association with the disease. No association between COVID-19 disease and the different AGTR1 SNPs was evidenced on multivariable, nevertheless the A/A genotype for rs5183 showed an higher hospitalization risk in patients with comorbidities.ConclusionsDifferent genetic variants in ACE2 were associated with a severe clinical course and death groups of patients with COVID-19. ACE2 common SNPs in the population might modulate severity of COVID-19 infection independently of other known markers like gender, age and comorbidities.

We studied an inception cohort of children with juvenile idiopathic arthritis (JIA) to (1) identify distinct disease courses based on changes over 5 years in 5 variables prioritized by patients, parents, and clinicians; and (2) estimate the probability of a severe disease course for each child at diagnosis. Assessments of quality of life, pain, medication requirements, patient-reported side effects, and active joint counts were scheduled at 0, 6, 12, 18, 24, 36, 48, and 60 months. Patients who attended at least 6 assessments were included. Multivariable cluster analysis, r2, and silhouette statistics were used to identify distinct disease courses. One hundred candidate prediction models were developed in random samples of 75% of the cohort; their reliability and accuracy were tested in the 25% not used in their development. Four distinct courses were identified in 609 subjects. They differed in prioritized variables, disability scores, and probabilities of attaining inactive disease and remission. We named them Mild (43.8% of children), Moderate (35.6%), Severe Controlled (9%), and Severe Persisting (11.5%). A logistic regression model using JIA category, active joint count, and pattern of joint involvement at enrollment best predicted a severe disease course (Controlled + Persisting, c-index = 0.87); 91% of children in the highest decile of risk actually experienced a severe disease course, compared to 5% of those in the lowest decile. Children in this JIA cohort followed 1 of 4 disease courses and the probability of a severe disease course could be estimated with information available at diagnosis.

Microcirculatory hemodynamic indexes (HI) were assessed in patients with moderate and severe COVID-19. In both groups, a significant increase in the absolute spectral indexes (HI1, HI2, and HI3) and the ratio of low-frequency to high-frequency component (HI1/HI3) was revealed. In the group of severe infection, only the “slow” index (low-frequency HI1) of microcirculatory hemodynamics was significantly lower. The oscillatory indices MAYER1-3 and RESP1-3 were reduced in patients of both groups. The aggravation of the disease course was accompanied by depression of the low-frequency index HI1. Regulatory shifts compensate for disturbances in microcirculatory processes in moderate COVID-19, but severe course was associated with their decompensation.

Abstract. The relevance of the study is due to the lack of data on the state of nonspecific cellular immunity in studies with sera and autostrains of S. aureus isolated from patients with allergic dermatoses, which would reflect the intensity of antimicrobial immunity in patients with allergic dermatoses, aggravated by staphylococcal infection, depending on the severity of dermatosis. The aim of the study was to determine and analyze the results of antimicrobial immunity indicators in patients with atopic dermatitis and true eczema, aggravated by staphylococcal infection, using sera and autostrains of S. aureus, depending on the severity of the disease. Material and methods. It was included 107 patients with different stage of the allergic dermatoses severity and control group of 15 healthy individuals to the research . The patients were divided into 3 groups in according to the severity of cutaneous process course. There were determined the basic indices of initial stages of phagocytosis and oxydepending bactericidal activity of the phagocytes. It was conducted the immunologic examinations using the autostrains patient from the locus morbi and standard strain S. aureus ATCC for the estimation of antimicrobial immunity. Results. Evaluation of phagocytosis indices in patients with allergodermatosеs showed a correlation between the severity of the disease course and the level of inhibition of the cellular level of nonspecific immunity. According to the results of studies using autostrains S. aureus, the most significant inhibition of phagocytosis (p ≤ 0,05), compared to the values of similar indicators in the control group of healthy individuals, it was found in the groups of patients with moderate and severe atopic dermatosis (AD) course, respectively: phagocytic activity (PhА) (78,1 ± 1,4) and (72,4 ± 1,4) and (71,7 ± 0,8) %; phagocytic number___ (PhN) (5,3 ± 0,2) and (4,3 ± 0,2) and (3,5 ± 0,1) absolute number (abs. num.); phagocytic index__ (PhI) (6,8 ± 0,2) and (6,2 ± 0,2) and (4,8 ± 0,1) abs. num.; phagocytic capacity (PhC) (30,3 ± 1,0) and (26,5 ± 1,8) and (22,6 ± 0,8) ×103 microbial cell /mm3; spontaneous test of the renovation of nitroblue tetrazolium (sNBT) (42,1 ± 1,3) and (48,1 ± 1,2) and (50,6 ± 0,3) %; induction test of the renovation of nitroblue tetrazolium (іNBT) (63,4 ± 1,6) and (53,4 ± 0,8) and (51,7 ± 0,7) %. In the patients with true eczema (TE), they revealed a similar regularity of phagocytosis inhibition, most pronounced in patients with a severe disease course (p ≤ 0,05), but with a slightly smaller degree of difference between the indicator values of phagocytosis compared with the group of healthy individuals, respectively: PhА (74,8 ± 1,3) and (78,1 ± 1,4) %; PhN (4,5 ± 0,1) and (5,3 ± 0,2) abs. num.; PhI (5,9 ± 0,2) and (6,8 ± 0,9) abs. num.; sНСТ (46,0 ± 0,6) and (42,1 ± 1,3) %; іНСТ (51,8 ± 0,8) and (63,4 ± 1,6) %. Conclusions. The results of identification of phagocytosis in patients with allergodermatosеs using the standard culture of S. aureus ATCC 25923 generally reflect the described regularities of inhibition in patients of the cellular level of nonspecific immunity, but are less presentable for their identification in comparison with the autostrains. Keywords: allergic dermatoses, severity of the course, S aureus autostrains, S. aureus ATCC 25923, antimicrobial resistance.