The role of mast cells and their proteases in lung damage associated with COVID-19.

The new coronavirus infection COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2, has posed scientific and public health challenges. The problem of treating COVID-19 still remains, and the pathogenesis of COVID-19 needs to be studied in detail, including the involvement of mast cells (MCs) and their specific proteases. The aim of this study was to characterize the role of mast cell proteases chymase, tryptase, and carboxypeptidase A3 (CPA3) in the lung damage associated with COVID-19. Methods. The study included postmortem lung biopsies from 30 patients who died of severe COVID-19, and biopsies from 9 control group patients. Histological preparations were made and protease profile and degranulation activity of MCs were analyzed. In addition, some demographic, clinical, and laboratory parameters were analyzed. Results. The average number of tryptase-positive MCs without evidence of degranulation and the total number of CPA3-positive MCs were statistically significantly higher in patients with COVID-19, and the number of tryptase-positive and CPA3-positive MCs fragments was lower compared with controls. Negative correlations were established between the numbers of tryptase-positive MCs and red blood cell count. Negative correlations were found between non-granulating tryptase-positive MCs and hemoglobin levels. Positive correlations were noted between tryptase-positive MCs and the leukocytes and eosinophils counts, and negative correlations were noted between the number of CPA3-positive cells and the platelet count. A positive correlation was found between the number of adjoining MCs, as well as fragments of tryptase-positive MCs, and the erythrocyte sedimentation rate (ESR). A negative correlation was also observed between the number of non-degranulated CPA3-positive MCs and the blood level of C-reactive protein. In patients with COVID-19, reduced degranulation activity of tryptase-positive MCs was found along with increased representation of CPA3-positive MCs. Several trends and associations with laboratory test results were noted. The potential involvement of MCs in the development of anemia and thrombocytopenia is considered. Associations were established between tryptase-positive MCs and the peripheral blood counts of leukocytes and eosinophils, as well as ESR. Conclusion. The results obtained are highly contradictory. Since many aspects of the involvement of MCs and their proteases in COVID-19 pathogenesis are still unknown, studies with larger cohorts of patients are needed.Copyright © Budnevsky A.V. et al., 2023.

Asthma in the elderly and COVID-19: results of the 90-day post-hospital follow-up.

Background. After the first wave of the new SARS-CoV-2 coronavirus infection, the researchers focused on identifying potential short-and long-term complications of COVID-19, especially in high-risk patients, after prolonged hospitalization and intensive care. Objective. To study the outcomes, adverse effects of severe COVID-19 and their predictors 90 days after hospital discharge in elderly patients with asthma. Material and methods. The study included elderly patients (101 subjects, 42 males and 59 females;median age 74 (67;79) years) with asthma, discharged from the hospital after treatment of severe COVID-19. They were followed up for 90 days after discharge. In the hospital, COVID-19 was confirmed by laboratory tests (polymerase chain reaction method) and/or clinically and radiologically. All patients had a documented history of asthma according to GINA 2020 criteria. Results and discussion. During the 90-day post-hospital follow-up, 86 (85%) patients survived, and 15 (15%) died after discharge. Deaths were reported within 1 to 4 weeks after discharge: 6 subjects died during re-hospitalization, 6 at home, and 3 in a rehabilitation center. The multivariate regression analysis model, adjusted for all statistically significant indicators, and the ROC analysis showed the most significant predictors of 90-day post-hospital mortality and their threshold values. They include the Charlson comorbidity index >=4 points, lung damage according to computed tomography >=30%, the absolute number of eosinophils <=100 cells/muL, and concomitant diabetes mellitus. The analysis showed that 90-day post-hospital mortality depends on combinations of identified risk factors;a combination of two, three, and especially four risk factors statistically significantly is associated with patients' lower average survival time. Conclusion. The key risk factors for 90-day post-hospital mortality in elderly patients with asthma after severe COVID-19 include the Charlson comorbidity index, lung damage >=30% according to computed tomography, the absolute number of eosinophils <=100 cells/muL, and concomitant diabetes mellitus. The 90-day post-hospital survival rate is correlated with the number of risk factors identified in patients. The effect of asthma severity on 90-day post-hospital mortality in elderly patients was not observed.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

[Risk factors for adverse outcomes in elderly patients with asthma and severe COVID-19 at the hospital and early post-hospital stages].

BACKGROUND: Mortality and COVID-19 related factors are thoroughly analyzed. Given the large number of hospitalized patients, the potential short- and long-term COVID-19 related complications, further research is needed on the possible consequences of hospitalization, especially in higher-risk patients, after prolonged hospitalization and intensive care admission. AIM: To study the clinical course and outcomes of severe COVID-19 in elderly patients with asthma at the hospital and early post-hospital stages. MATERIALS AND METHODS: The study included 131 elderly patients (WHO, 2020) >60 years old, n=131 with asthma, hospitalized for severe COVID-19. Of these, 86 (65.6%) patients survived, 30 (22.9%) died in the hospital, and 15 (14.9%) patients died after discharge from the hospital (in the 90-day post-hospital period). COVID-19 was confirmed by laboratory tests (SARS-CoV-2 PCR RNA test) and/or clinically and radiologically. All patients had a documented history of asthma. Patients were followed up during the hospital stay and for 90 days after discharge. RESULTS: Comparison of outcomes showed that in the groups of patients with a fatal outcome (regardless of the stage), the Charlson comorbidity index, respiratory rate, extent of lung damage assessed by computed tomography, the absolute leukocyte and neutrophil number and the ratio of neutrophils to lymphocytes were statistically significantly higher. The absolute number of eosinophils was lower in these groups. In the group of patients who died during hospitalization, severe (IV-V) asthma (p=0.03), steroid use during the previous year (p=0.02), chronic heart failure with a reduced ejection fraction (p=0.009) were more common, and atopic asthma phenotype was less common (p=0.02). In those who died after discharge, more common were non-invasive ventilation and diabetes mellitus (p<0.001). The multivariate regression analysis model revealed the most significant predictors of mortality at the hospital and early post-hospital stages. CONCLUSION: Adverse outcomes of severe COVID-19 in elderly patients with asthma include hospital and post-hospital mortality. The most significant predictors of mortality are the comorbidity index and low eosinophil count. Hospital mortality is associated with a higher ratio of neutrophils to lymphocytes and lower total protein levels; early (90-day) post-hospital mortality is associated with extensive lung damage shown by computed tomography and diabetes mellitus.

The role of mast cells and their proteases in lung damage associated with COVID-19.

The new coronavirus infection COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2, has posed scientific and public health challenges. The problem of treating COVID-19 still remains, and the pathogenesis of COVID-19 needs to be studied in detail, including the involvement of mast cells (MCs) and their specific proteases. The aim of this study was to characterize the role of mast cell proteases chymase, tryptase, and carboxypeptidase A3 (CPA3) in the lung damage associated with COVID-19. Methods. The study included postmortem lung biopsies from 30 patients who died of severe COVID-19, and biopsies from 9 control group patients. Histological preparations were made and protease profile and degranulation activity of MCs were analyzed. In addition, some demographic, clinical, and laboratory parameters were analyzed. Results. The average number of tryptase-positive MCs without evidence of degranulation and the total number of CPA3-positive MCs were statistically significantly higher in patients with COVID-19, and the number of tryptase-positive and CPA3-positive MCs fragments was lower compared with controls. Negative correlations were established between the numbers of tryptase-positive MCs and red blood cell count. Negative correlations were found between non-granulating tryptase-positive MCs and hemoglobin levels. Positive correlations were noted between tryptase-positive MCs and the leukocytes and eosinophils counts, and negative correlations were noted between the number of CPA3-positive cells and the platelet count. A positive correlation was found between the number of adjoining MCs, as well as fragments of tryptase-positive MCs, and the erythrocyte sedimentation rate (ESR). A negative correlation was also observed between the number of non-degranulated CPA3-positive MCs and the blood level of C-reactive protein. In patients with COVID-19, reduced degranulation activity of tryptase-positive MCs was found along with increased representation of CPA3-positive MCs. Several trends and associations with laboratory test results were noted. The potential involvement of MCs in the development of anemia and thrombocytopenia is considered. Associations were established between tryptase-positive MCs and the peripheral blood counts of leukocytes and eosinophils, as well as ESR. Conclusion. The results obtained are highly contradictory. Since many aspects of the involvement of MCs and their proteases in COVID-19 pathogenesis are still unknown, studies with larger cohorts of patients are needed.Copyright © Budnevsky A.V. et al., 2023.

Asthma in the elderly and COVID-19: results of the 90-day post-hospital follow-up.

Background. After the first wave of the new SARS-CoV-2 coronavirus infection, the researchers focused on identifying potential short-and long-term complications of COVID-19, especially in high-risk patients, after prolonged hospitalization and intensive care. Objective. To study the outcomes, adverse effects of severe COVID-19 and their predictors 90 days after hospital discharge in elderly patients with asthma. Material and methods. The study included elderly patients (101 subjects, 42 males and 59 females;median age 74 (67;79) years) with asthma, discharged from the hospital after treatment of severe COVID-19. They were followed up for 90 days after discharge. In the hospital, COVID-19 was confirmed by laboratory tests (polymerase chain reaction method) and/or clinically and radiologically. All patients had a documented history of asthma according to GINA 2020 criteria. Results and discussion. During the 90-day post-hospital follow-up, 86 (85%) patients survived, and 15 (15%) died after discharge. Deaths were reported within 1 to 4 weeks after discharge: 6 subjects died during re-hospitalization, 6 at home, and 3 in a rehabilitation center. The multivariate regression analysis model, adjusted for all statistically significant indicators, and the ROC analysis showed the most significant predictors of 90-day post-hospital mortality and their threshold values. They include the Charlson comorbidity index >=4 points, lung damage according to computed tomography >=30%, the absolute number of eosinophils <=100 cells/muL, and concomitant diabetes mellitus. The analysis showed that 90-day post-hospital mortality depends on combinations of identified risk factors;a combination of two, three, and especially four risk factors statistically significantly is associated with patients' lower average survival time. Conclusion. The key risk factors for 90-day post-hospital mortality in elderly patients with asthma after severe COVID-19 include the Charlson comorbidity index, lung damage >=30% according to computed tomography, the absolute number of eosinophils <=100 cells/muL, and concomitant diabetes mellitus. The 90-day post-hospital survival rate is correlated with the number of risk factors identified in patients. The effect of asthma severity on 90-day post-hospital mortality in elderly patients was not observed.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

Spectral analysis of cough sounds of patients with COVID-19.

Cough is a frequent manifestation of COVID-19 (COronaVIrus Disease 2019), therefore, it has an important diagnostic value. There is little information about the characteristics of cough of COVID-19 patients in the literature. To perform a spectral analysis of cough sounds in COVID-19 patients in comparison with induced cough of healthy individuals. Methods. The main group consisted of 218 COVID-19 patients (48.56% - men, 51.44% - women, average age 40.2 (32.4;50.1) years). The comparison group consisted of 60 healthy individuals (50.0% men, 50.0% women, average age 41.7 (31.2;53.0) years) who were induced to cough. Each subject had a cough sound recorded, followed by digital processing using a fast Fourier transform algorithm. The temporal-frequency parameters of cough sounds were evaluated: duration (ms), the ratio of the energy of low and medium frequencies (60 - 600 Hz) to the energy of high frequencies (600 - 6 000 Hz), the frequency of the maximum sound energy (Hz). These parameters were determined in relation to both the entire cough and individual phases of the cough sound. Results. Significant differences were found between some cough parameters in the main group and in the comparison group. The total duration of the coughing act was significantly shorter in patients with COVID-19, in contrast to the induced cough of healthy individuals (T = 342.5 (277.0;394.0) - in the main group;T (c) = 400.5 (359.0;457.0) - in the comparison group;p = 0.0000). In addition, it was found that the cough sounds of COVID-19 patients are dominated by the energy of higher frequencies as compared to the healthy controls (Q = 0.3095 (0.223;0.454) - in the main group;Q (c) = 0.4535 (0.3725;0.619) - in the comparison group;p = 0.0000). The maximum frequency of cough sound energy in the main group was significantly higher than in the comparison group (Fmax = 463.0 (274.0;761.0) - in the main group;Fmax = 347 (253.0;488.0) - in the comparison group;p = 0.0013). At the same time, there were no differences between the frequencies of the maximum energy of cough sound of the individual phases of cough act and the duration of the first phase. Conclusion. The cough of patients with COVID-19 is characterized by a shorter duration and a predominance of high-frequency energy compared to the induced cough of healthy individuals.Copyright © 2022 Budnevsky A.V. et al.

Spectral analysis of cough sounds of patients with COVID-19

Cough is a frequent manifestation of COVID-19 (COronaVIrus Disease 2019), therefore, it has an important diagnostic value. There is little information about the characteristics of cough of COVID-19 patients in the literature. To perform a spectral analysis of cough sounds in COVID-19 patients in comparison with induced cough of healthy individuals. Methods. The main group consisted of 218 COVID-19 patients (48.56% - men, 51.44% - women, average age 40.2 (32.4;50.1) years). The comparison group consisted of 60 healthy individuals (50.0% men, 50.0% women, average age 41.7 (31.2;53.0) years) who were induced to cough. Each subject had a cough sound recorded, followed by digital processing using a fast Fourier transform algorithm. The temporal-frequency parameters of cough sounds were evaluated: duration (ms), the ratio of the energy of low and medium frequencies (60 - 600 Hz) to the energy of high frequencies (600 - 6 000 Hz), the frequency of the maximum sound energy (Hz). These parameters were determined in relation to both the entire cough and individual phases of the cough sound. Results. Significant differences were found between some cough parameters in the main group and in the comparison group. The total duration of the coughing act was significantly shorter in patients with COVID-19, in contrast to the induced cough of healthy individuals (T = 342.5 (277.0;394.0) - in the main group;T (c) = 400.5 (359.0;457.0) - in the comparison group;p = 0.0000). In addition, it was found that the cough sounds of COVID-19 patients are dominated by the energy of higher frequencies as compared to the healthy controls (Q = 0.3095 (0.223;0.454) - in the main group;Q (c) = 0.4535 (0.3725;0.619) - in the comparison group;p = 0.0000). The maximum frequency of cough sound energy in the main group was significantly higher than in the comparison group (Fmax = 463.0 (274.0;761.0) - in the main group;Fmax = 347 (253.0;488.0) - in the comparison group;p = 0.0013). At the same time, there were no differences between the frequencies of the maximum energy of cough sound of the individual phases of cough act and the duration of the first phase. Conclusion. The cough of patients with COVID-19 is characterized by a shorter duration and a predominance of high-frequency energy compared to the induced cough of healthy individuals.

[Treatment of cicatricial tracheal stenosis and tracheoesophageal fistula in patients with COVID-19 pneumonia]. / Lechenie rubtsovogo stenoza trakhei i trakheopishchevodnogo svishcha u bol'nykh, perenesshikh COVID-19-pnevmoniyu.

OBJECTIVE: To describe treatment of cicatricial tracheal stenosis and tracheoesophageal fistula in patients with COVID-19 pneumonia. MATERIAL AND METHODS: There were 91 patients with cicatricial tracheal stenosis for the period from August 2020 to April 2022 (21 months). Of these, 32 (35.2%) patients had cicatricial tracheal stenosis, tracheoesophageal fistula and previous coronavirus infection with severe acute respiratory syndrome. Incidence of iatrogenic tracheal injury following ventilation for viral pneumonia in the pandemic increased by 5 times compared to pneumonia of other genesis. Majority of patients had pneumonia CT grade 4 (12 patients) and grade 3 (8 patients). Other ones had pulmonary parenchyma lesion grade 2-3 or mixed viral-bacterial pneumonia. Isolated tracheoesophageal fistula without severe cicatricial stenosis of trachea or esophagus was diagnosed in 4 patients. In other 2 patients, tracheal stenosis was combined with tracheoesophageal fistula. Eight (25%) patients had tracheostomy at the first admission. This rate was almost half that of patients treated for cicatricial tracheal stenosis in pre-pandemic period. RESULTS: Respiratory distress syndrome occurred in 1-7 months after discharge from COVID hospital. All patients underwent surgery. In 7 patients, we preferred palliative treatment with dilation and stenting until complete rehabilitation. In 5 patients, stent was removed after 6-9 months and these ones underwent surgery. There were 3 tracheal resections with anastomosis, and 2 patients underwent tracheoplasty. Resection was performed in 3 patients due to impossible stenting. Postoperative course in these patients was standard and did not differ from that in patients without viral pneumonia. In case of tracheoesophageal fistula, palliative interventions rarely allowed isolation of trachea. Four patients underwent surgery through cervical approach. There were difficult surgeries in 2 patients with tracheoesophageal fistula and cicatricial tracheal stenosis. One of them underwent separation of fistula and tracheal resection via cervical approach at primary admission. In another patient with thoracic fistula, we initially attempted to insert occluder. However, open surgery was required later due to dislocation of device. CONCLUSION: Absolute number of patients with tracheal stenosis, tracheoesophageal fistula and previous COVID-19 has increased by several times compared to pre-pandemic period. This is due to greater number of patients requiring ventilation with risk of tracheal injury, non-compliance with preventive protocol for tracheal injury including anti-ischemic measures during mechanical ventilation. The last fact was exacerbated by involvement of allied physicians with insufficient experience of safe ventilation in the «red zone¼, immunodeficiency in these patients aggravating purulent-inflammatory process in tracheal wall. The number of patients with tracheostomy was 2 times less that was associated with peculiarity of mechanical ventilation in SARS-CoV-2. Indeed, tracheostomy was a poor prognostic sign and physicians tried to avoid this procedure. Incidence of tracheoesophageal fistula in these patients increased by 2 times compared to pre-pandemic period. In subacute period of COVID-associated pneumonia, palliative measures for cicatricial tracheal stenosis and tracheoesophageal fistula should be preferred. Radical treatment should be performed after 3-6 months. Absolute indication for circular tracheal resection with anastomosis is impossible tracheal stenting and ensuring safe breathing by endoscopic methods, as well as combination of cicatricial tracheal stenosis with tracheoesophageal fistula and resistant aspiration syndrome. Incidence of postoperative complications in patients with cicatricial tracheal stenosis and previous mechanical ventilation for COVID-19 pneumonia and patients in pre-pandemic period is similar.

Analysis of severity and evaluation of prognosis in elderly patients with bronchial asthma and severe COVID-19

Introduction. The role of comorbid conditions in susceptibility to SARS-CoV-2 infection and the severity of associated COVID-19 disease has been an area of ongoing research since the pandemic began. Objective. To evaluate the impact of elderly asthma on the clinical course and outcomes of severe COVID-19. Materials and methods. Elderly patients (WHO, 2020) (> 60 years, n = 131) with bronchial asthma (BA) hospitalized for severe COVID-19 were included in the study. The presence of COVID-19 was confirmed by laboratory tests (PCR smear) and/or clinical and radiological examinations. All patients had a history of a confirmed diagnosis of bronchial asthma (GINA, 2020). Follow-up was performed at the hospital stage and for 90 days after discharge from the hospital. Results. In the groups of patients with lethal outcome (regardless of the stage) there were statistically significantly higher Charlson index, respiratory rate, CT lung lesion volume, leukocyte, neutrophil and neutrophil to lymphocyte ratios, lower absolute eosinophil count. In the group of patients who died during hospitalization, severe (IV–V) asthma (p = 0.03), steroid use during the previous year (p = 0.02), chronic heart failure (p = 0.009), and the atopic asthma phenotype was less common (p = 0.02). Those who died in the 90-day posthospital period had greater lung lesion volume on CT scan, and diabetes mellitus was more common (p < 0.001). The most significant predictors of mortality were identified. Conclusion. The common most significant predictors of hospital and 90-day posthospital mortality in older patients with bronchial asthma were comorbidity index and lower eosinophil levels. Hospital mortality is further characterized by a higher neutrophil to lymphocyte ratio and lower total protein;90-day posthospital mortality by the amount of lung damage on CT scan and the presence of diabetes mellitus. © 2022, Remedium Group Ltd. All rights reserved.

Analysis of severity and evaluation of prognosis in elderly patients with bronchial asthma and severe COVID-19

Introduction. The role of comorbid conditions in susceptibility to SARS-CoV-2 infection and the severity of associated COVID-19 disease has been an area of ongoing research since the pandemic began. Objective. To evaluate the impact of elderly asthma on the clinical course and outcomes of severe COVID-19. Materials and methods. Elderly patients (WHO, 2020) (> 60 years, n = 131) with bronchial asthma (BA) hospitalized for severe COVID-19 were included in the study. The presence of COVID-19 was confirmed by laboratory tests (PCR smear) and/or clinical and radiological examinations. All patients had a history of a confirmed diagnosis of bronchial asthma (GINA, 2020). Follow-up was performed at the hospital stage and for 90 days after discharge from the hospital. Results. In the groups of patients with lethal outcome (regardless of the stage) there were statistically significantly higher Charlson index, respiratory rate, CT lung lesion volume, leukocyte, neutrophil and neutrophil to lymphocyte ratios, lower absolute eosinophil count. In the group of patients who died during hospitalization, severe (IV–V) asthma (p = 0.03), steroid use during the previous year (p = 0.02), chronic heart failure (p = 0.009), and the atopic asthma phenotype was less common (p = 0.02). Those who died in the 90-day posthospital period had greater lung lesion volume on CT scan, and diabetes mellitus was more common (p < 0.001). The most significant predictors of mortality were identified. Conclusion. The common most significant predictors of hospital and 90-day posthospital mortality in older patients with bronchial asthma were comorbidity index and lower eosinophil levels. Hospital mortality is further characterized by a higher neutrophil to lymphocyte ratio and lower total protein;90-day posthospital mortality by the amount of lung damage on CT scan and the presence of diabetes mellitus. © 2022, Remedium Group Ltd. All rights reserved.

COVID-19 in Russia: Evolution of Views on the Pandemic. Report II

Over the two years of the novel coronavirus infection (COVID-19) pandemic, there has been an evolution of views in various fields of medicine, which has led to a powerful development of scientific research in the field of epidemiology, clinic, diagnosis and therapy of COVID-19. This article discusses the evolution of views and approaches to the study of the clinic and therapy of COVID-19. The symptoms and aggravation of the course of cardiovascular diseases with COVID-19 have been established. The main strategy for organizing surgical care for patients with COVID-19 is indicated. The main criteria for the treatment of COVID-19, the need to prescribe SGCS on an individual basis, and the need to search for new methods of anti-inflammatory therapy for COVID-19, one of which may be the use of alkylating drugs in ultra-low doses, are described. Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

USING COVID-GLOBULIN IN COVID-19 TREATMENT

Under auspices of the Eurasian Association of Therapists (EUAT), a Council of Experts (COE) was organized to develop criteria for the timing of administration (day of illness onset) of COVID-globulin, dosing regimens and patient phenotypes depending on comorbid pathology to optimize indications and achieve maximum effectiveness of virus-neutralizing therapy. The need for COE creation is related to the lack of criteria based on large-scale evidence-based studies. That is why the working group of COE includes experts in all fields of internal medicine, in particular, transfusiology specialists. The COE activity was held with the participation of largest plasma transfusion centers for recuperative patients including Clinical Hospitals No. 40 and 52 of the Moscow City Government Department of Health, and the N. V. Sklifosovsky Institute of Emergency Medicine. Copyright © 2022 Authors. All rights reserved.

Rehabilitation after COVID-19. Resolution of the International Expert Council of the Eurasian Association of Therapists and the Russian Society of Cardiology

By the middle of 2021, the official global number of coronavirus disease 2019 (COVID-19) patients was close to 230 million, but the number accounting for asymptomatic patients was much higher. Consequences and rehabilitation after COVID-19 are of particular interest and raise many controversial and unresolved issues. On May 18, 2021, the Eurasian Association of Therapists organized an international panel of experts to analyze challenges associated with the post-COVID-19 period. This panel aimed to develop approaches to identify gaps in the discussed issues. This interdisciplinary team of leading experts reviewed the current literature and presented their data to formulate practical guidance on management of patients after COVID-19. The panel of experts also presented recommendations on how to implement the gained knowledge into health care practices. Copyright © 2021, Silicea-Poligraf. All rights reserved.

COVID-19 in Russia: Evolution of Views on the Pandemic. Report I

Over the two years of the novel coronavirus infection (COVID-19) pandemic, there has been an evolution of views in various fields of medicine, which has led to a powerful development of scientific research in the field of epidemiology, clinic, diagnosis and therapy of COVID-19. The article highlights the evolution of views and approaches to the study of the epidemiology and radiology of COVID-19. The data of molecular genetic studies are shown, which are the most important component of epidemiological surveillance. The study of the manifestations of the COVID-19 epidemic process made it possible to distinguish two stages in the development of the epidemiological situation in the Russian Federation. At the first stage of the epidemic, two rises in the incidence rate of the population were recorded, regulated by social and natural factors. The second stage of the epidemic was due to a change in the biological properties of the SARS-CoV-2 virus, followed by a change in the prevailing genovariants (Alpha, Delta and Omicron). At the second stage of the epidemic, three rises in the incidence of the population were recorded. The general principles for the use of radiodiagnosis methods, which are used primarily to detect lung damage in COVID-19, are given. With the accumulation of experience, a natural change in ideas about the algorithms for the use of visualization technologies has occurred. Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

Asthma and COVID-19 in the elderly: course, survival, predictors of mortality

Bronchial asthma occurs in 0.9 - 17% of patients hospitalized with COVID-19. However, it is not clear whether asthma is a risk factor for the development and severity of COVID-19. Studies have shown that patients with asthma appear to be more susceptible to COVID-19 infection, but severe disease progression is not related to medication use, including asthma biologics, but rather to older age and comorbidities. Aim. To evaluate the clinical course of SARS-CoV-2 infection in elderly patients with asthma, to examine the effect of asthma and comorbidities on COVID-19-related outcomes, and to determine predictors of mortality. Methods. Elderly patients [WHO, 2020] (> 60 years, n = 131, median age 74 (67;80) years;59 men, 72 women) with asthma hospitalized for COVID-19 were included in the study. COVID-19 was confirmed by laboratory tests (PCR smear) and/or clinical and radiological examinations. All patients had a history of a documented diagnosis of asthma (GINA, 2020). Results. Out of 131 patients, 30 (22.9%) died in the hospital, and 15 (14.9%) died after discharge from the hospital (within 90 days). The group of patients with lethal outcome showed the following differences from those who recovered: values of Charlson index, respiration rate, degree of lung damage on CT scan, absolute number of leukocytes, neutrophils and neutrophils-to-lymphocytes ratio, C-reactive protein on the 5th day of hospitalization, and LDH were statistically significantly higher, while absolute number of eosinophils, total protein content, SpO2 and SpO2/FiO2 levels were lower;steroid intake during the year and non-atopic asthma were more common. Multivariate and ROC analysis revealed the most significant predictors of hospital mortality and their thresholds: Charlson comorbidity index ≥ 6 points, neutrophil/lymphocyte ratio ≥ 4.5, total protein ≤ 60 g/l, eosinophil level ≤ 100 cells/μL. Conclusion. The most significant predictors of hospital mortality in elderly patients with severe COVID-19 against asthma are Charlson comorbidity, neutrophil/lymphocyte ratio;lower eosinophil and total protein levels. Survival time of patients has an inverse correlation with the number of mortality risk factors present.

Forecast of the socioeconomic burden of COPD in the Russian Federation in 2022

Chronic obstructive pulmonary disease (COPD) is characterized by a high level of morbidity and mortality and is associated with significant social and economic losses for the health care system and society. Aim. To predict the socio-economic burden of COPD in the Russian Federation in 2022, including the cost of drug treatment. Methods. The socio-economic burden of COPD in the Russian Federation in 2022 was predicted with and without taking into account the impact of COVID-19. The analysis of the cost of illness included the calculation of direct and indirect costs due to COPD. Data of Federal State Statistics Service, the State Guarantee Program of Free Medical Care for Citizens of Russian Federation, and data from the regional register of drug treatment of patients with COPD were used. Costs of medical care (ambulatory, hospital, and emergency care) were calculated based on compulsory health insurance tariffs. The disability benefits payments were calculated based on number of disabled persons and the amount of the disability benefit in each group. Indirect costs (or economic losses) included losses from products which were not produced due to disability and premature mortality of working-aged adults. Results. The predicted total economic losses due to COPD in 2022 will be 428.5 billion rubles when taking into account the impact of COVID-19, and 378.9 billion rubles when not accounting for COVID-19. Losses in the economy due to decreased labor productivity because of premature deaths (86%) are major part of the main burden. The cost of drug therapy for patients with COPD in outpatient settings will amount to over 17 billion rubles. Conclusion. Potential economic burden of COPD in 2022 depends on the incidence of COVID-19 and could be 0.34% of the GDP. Priority should be given to measures aimed at preventing the occurrence of COPD by correcting risk factors in the population, early diagnosis, slowing the progression of the disease and preventing exacerbations. Prevention of respiratory infections including COVID-19 in patients with COPD plays a special role.

COVID-19: Opportunities to Improve Prognosis.

COVID-19 is characterized by a severe course in approximately 5‒10% of patients, who require admittance to the intensive care unit and mechanical ventilation, which is associated with a very high risk of a poor prognosis. At present, in real clinical practice, in managing severe patients with COVID-19, noninvasive ventilation (NIV) is widely used (in some countries, up to 60% of all methods of respiratory support). In most studies on the effectiveness of NIV in hypoxemic acute respiratory failure in patients with COVID-19, the need for tracheal intubation and hospital mortality with the use of NIV averaged 20-30%, which suggests the rather high efficiency of this method. The COVID-19 pandemic has given a powerful impetus to the widespread use of prone positioning among nonintubated patients with acute respiratory failure caused by COVID-19. Several studies have shown that prone positioning can reduce the need for mechanical ventilation and hospital mortality. Medications that have proven effective in severe forms of COVID-19 include remdesivir, systemic glucocorticoids, tocilizumab, baricitinib, and anticoagulants. Among the new promising areas of drug therapy, noteworthy is the use of thiol-containing drugs (N-acetylcysteine), inhaled surfactant, and inhaled prostacyclin analogues.

N-acetylcysteine as a therapeutic approach to post-COVID-19 pulmonary fibrosis adjunctive treatment.

OBJECTIVE: Growing interest is directed to the outcomes of COVID-19 in survivors, both in the convalescent period and in the long-term, which are responsible for morbidity and quality of life deterioration. This article aims to describe the mechanisms supporting the possible use of NAC as an adjuvant treatment for post-COVID-19 pulmonary fibrosis. MATERIALS AND METHODS: A search was performed in PubMed/MEDLINE. RESULTS: Interstitial changes have been observed in the CT scan of COVID-19 pneumonia. In patients with respiratory outcomes in the post-COVID-19 stage, glutathione (GSH) deficiency was found and interpreted as a reaction to the inflammatory cascade caused by the viral infection, while the pathophysiological process of pulmonary fibrosis involves numerous cytokines, such as TGF-ß, TNF-α, IL-1, PDGF and VEGF. NAC has a good tolerability profile, is easily administered orally and inexpensively, and has antioxidant and anti-inflammatory effects that may target the pathophysiologic mechanisms involved in pulmonary fibrosis. It may revert GSH deficiency, exerts direct and indirect antioxidant activity, anti-inflammatory activity and improves immune T-cell response. CONCLUSIONS: The mechanism of action of NAC suggests a role in the treatment of pulmonary fibrosis induced by COVID-19.

Use of nonsteroidal antiinflammatory drugs during the COVID19 pandemic. Resolution of the Expert Council of the Russian Society for the Prevention of Noncommunicable Diseases

The spread and consequences of the coronavirus disease 2019 (COVID19) pandemic are currently one of the most pressing public health challenges in the world. Despite the fact that experience accumulates in the treatment and monitoring of COVID19 patients, certain aspects are still a clinical dilemma. In particular, this regarded the use of nonsteroidal antiinflammatory drugs (NSAIDs) during the pandemic, both as a symptomatic treatment of infection, and in patients with comorbidities requiring NSAID. A series of studies did not establish evidence of the risk of infection and complications from NSAID therapy in COVID19. At the same time, the practitioner should take into account the risk of specific NSAIDassociated complications, which also remain relevant during the COVID19 pandemic. This resolution focuses on the evolution of ideas about NSAID use and safety in COVID19, and also emphasizes the particular relevance of their use for a number of clinical situations. © 2022 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved.

The outpatient medical care in patients with chronic diseases under dispensary supervision in the conditions of the COVID19 pandemic. Temporary guidelines. Version 2

The aim of these guidelines is to provide primary care physicians with scientifically based algorithms for the implementation of dispensary monitoring in patients with chronic noncommunicable diseases in the conditions of the new coronavirus infection (COVID19) pandemic, including the use of telemedicine technologies. The organization and conduct of highquality medical followup are the most important tasks aimed at both reducing the risks of developing complications of chronic noncommunicable diseases and reducing overall mortality, especially in the current conditions of the COVID19 pandemic. The guidelines contain clinical aspects of dispensary followup, general principles of tactics for managing patients with various chronic noncommunicable diseases in COVID19 conditions, in addition, brief checklists with options for interviewing patients with various chronic noncommunicable diseases are presented, topical aspects of the interaction of drugs used in the treatment of chronic noncommunicable diseases with antiviral drugs are considered. The guidelines are intended for general practitioners, district therapists, general practitioners (family doctors), as well as doctors of other specialties providing primary health care. © 2022 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved.