Invasive aspergillosis in patients with COVID-19 in intensive care units: results of a multicenter study.

Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Prevention of vitamin D deficiency in children. The state of the problem in the world and in Ukraine.

The article presents current data on the prevalence of vitamin D deficiency and criteria for its deficiency in children in different countries. Vitamin D is recognized as one of the most important vitamins involved in many biochemical processes in the body. Its active metabolites play a key role in calcium absorption, bone mineralization and promote phosphate and magnesium metabolism. At the same time, in addition to affecting mineral metabolism, there is a wide range of conditions in which vitamin D also plays a preventive role. Vitamin D has been shown to play a vital role in innate immunity maintenance and is important in prevention of several diseases, including infections, autoimmune diseases, certain forms of cancer, type 1 and 2 diabetes, and cardiovascular diseases. Vitamin D is of particular importance for newborns and young children. This vitamin is involved in important physiological regulatory processes such as bone metabolism, lung development, maturation of the immune system and differentiation of the nervous system. Vitamin D deficiency increases risks of neonatal sepsis, necrotizing enterocolitis, respiratory distress syndrome, and bronchopulmonary dysplasia. Adequate intake of vitamin D and calcium during childhood can reduce the risk of osteoporosis and other diseases associated with vitamin D deficiency in adults. Recently, vitamin D deficiency has shown to be a potential risk factor for COVID-19 propensity. It has been established that to date most scientific pediatric societies have recognized the need to prevent vitamin D deficiency in healthy children of all ages, but data on the dosage of vitamin D in its prophylactic use differ. Most scientific societies recommend an average of 400-600 IU per day of vitamin D for prophylactic purposes. The analysis of published data shows the need to follow a strategy based on an individual approach, taking into account physiological characteristics, individual requirements and lifestyle.Copyright © 2021 University of Tartu Press. All rights reserved.

Pediatric Inflammatory Multisystem Syndrome Temporally Associated with Sars-Cov-2 Infection

Despite the low incidence, low mortality and relatively mild symptoms of COVID-19 in children, there has been a rise in pediatric patients who develop a condition resembling Kawasaki disease after COVID-19 or contact with individuals infected with SARS-CoV-2. This condition is known as the pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS). This review introduces the reader to the hypotheses of PIMS-TS pathogenesis, provides information about its diagnosis and treatment, presents clinical and laboratory data and describes treatments strategies used in children and adolescents hospitalized to the intensive care unit of the Pediatric Research and Clinical Center for Infectious Diseases. Besides, the review outlines the main diagnostic and prognostic challenges of PIMS-TS.Copyright © Extreme Medicine.All right reserved.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review.

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.

Development of a practical guide to infectious diseases with elements of digital technologies

A doctor of any specialty in his practice is faced with an infectious pathology, in connection with which the early diagnosis of infectious diseases is important both from a clinical and epidemiological standpoint. The aim - design and development of a unified practical guide to infectious diseases with elements of digitalization of content on pharmacotherapy. Material and methods. When developing the structure of the practical guide "Tactics of an infectious disease doctor", prototypes of educational and methodological materials were worked out. The structure of the practical guide included socially significant infectious diseases of viral, bacterial etiology, the most important helminthiases and protozoses, which practitioners of various specialties may encounter, both in inpatient and outpatient settings. Results and discussion. In the practical guide "Tactics of an infectious disease doctor" all nosologies are presented in a unified form: a brief definition of nosologies, characteristics of the etiological agent, epidemic process, clinical classification, examples of the formulation of a diagnosis, diagnosis, organization of medical care, treatment, pharmacotherapy, approximate terms of temporary disability, criteria recovery, rehabilitation, dispensary observation, recommendations for treatment and prevention. The practical guide contains a short guide to medicines. An innovation is the presentation of medicines via a QR code. Also, by means of a QR code, it is possible to switch to the electronic version of the practical guide. Recommendations for the prevention of infectious diseases are given in the form of pictographic diagrams. Conclusion. The practical guide "Tactics of an infectious disease doctor" allows primary care physicians and general practitioners in a short time period to make the optimal decision on the tactics of managing patients with infectious diseases, within the framework of modern clinical guidelines and approaches set out in national guidelines.Copyright © 2021 Infectious Diseases: News, Opinions, Training. All rights reserved.

[Clinico-psychological profile and life quality of patients with post-COVID syndrome]. / Kliniko-psikhologicheskii profil' i kachestvo zhizni patsientov s postkovidnym sindromom.

OBJECTIVE: To study clinico-psychological profile and life quality of patients with post-COVID syndrome. MATERIAL AND METHODS: We examined 162 patients aged 24-60 years with confirmed SARS-CoV-2 infection which having symptoms that served as the basis for the diagnosis of post-COVID syndrome. Patients underwent general neurological and somatic examination with allocation of the corresponding neurological syndromes. The intensity and quality of pain were assessed using the McGill Pain questionnaire. The level of psychosocial stress was determined by the Holmes-Ray questionnaire, the identification and severity of asthenia - by the MFI-20 asthenia scale. The level of reactive and personal anxiety was studied according to the Spielberger-Khanin questionnaire, depression - according to the Beck scale. The assessment of life quality was carried out using the Russian version of SF-36 questionnaire. To correct the identified disorders, Mexidol was used according to the scheme: 500 mg once daily intravenously for 14 days, followed by Mexidol FORTE 250 750 mg per day orally (250 mg 3 times a day) for 2 months. RESULTS: The course of treatment with Mexidol in patients with post-COVID syndrome led to decrease in the severity of subjective and objective symptoms, asthenic, anxiety and depressive disorders, and improved the life quality of patients. CONCLUSION: The high efficacy and safety of sequential therapy with Mexidol (injections followed by tablets of Mexidol FORTE 250) has been shown.

Mitral valve chordal rupture against the background of cardiac SARS-CoV-2 infection. Cases series.

In an ever-changing information flow on coronavirus disease 2019 by the fact that the infection symptoms were mild, followed by signs (COVID-19) pandemic, we describe a case series of mitral valve chordal of probable endomyocarditis, unrecognized in time, and acute mitral rupture (MVCR) in non-comorbid middle-aged men that occurred over valve regurgitation developed against the background of physical a period of 3 to 5 weeks after Severe Acute Respiratory Syndrome provocation (exercise and cough). Two patients had previously been CoronaVirus 2 (SARS-CoV-2) infection. With significant advances diagnosed with mitral valve prolapse (myxomatous degeneration in the prevention of acute rheumatic fever, the treatment of bacterial and connective tissue disease). Two patients were successfully endocarditis and acute coronary syndrome, acute mitral regurgitation operated on in different clinics. The described cases emphasize that has become a relatively rare diagnosis. During the pandemic, there has the consequences of inflammation persistence may be more severe been a surge in the incidence of spontaneous MVCR, and new data on than the primary viral damage, which determines the importance of a the problem are accumulating. The presented case series are united comprehensive examination and long-term follow-up. To date, the differential diagnosis of patients with sudden onset of dyspnea and chest pain associated with an infectious process should include MVCR.Copyright © 2023 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved.

PERICARDIAL INVOLVEMENT ASSOCIATED WITH SARS-COV-2 INFECTION. PROSPECTIVE OBSERVATION IN THE COVID- WARD

Purpose. To identify the occurrence and structure of changes in the pericardium ultrasonography among patients who have undergone COVID-19 and have cardiological symptoms, as well as to compare these changes with the pericarditis aspects and the infection time duration in a prospective cohort observational study. Methods. Inclusion/exclusion criteria: current or transferred COVID-19, new symptoms that occurred during or after infection and forced to consult a cardiologist, the absence of other prerequisites for pericarditis and vaccination against SARS-CoV-2. Echocardiography was performed with an emphasis on the pericardium and an assessment of the echogenicity amplification, the area of the hyperechoic zone, thickness and artifacts, as well as a questionnaire. Results. From 05.2020 to On 10.2020, 335 patients from the covid ward and 284 patients from the out-patient clinic were included. 86% of patients had transient chest discomfort. The peaks of treatment accrued to 4-5 and 10-11 weeks (Me 10[2-36] (1 to 64) weeks) from SARS-CoV-2 infection occurred. Typical ECG changes were registered in 3%, pericardial friction noise – in 7% of patients. In 20% of patients discomfort in the heart area was the first, in 27% – the dominant, in 14% – the only symptom of COVID-19. According to EchoCG data, 96% of the examined patients had ultrasound signs of different changes in the pericardium: slight effusion in 65%, signs of tamponade in 2%, thickening in 12%, local hyperechogenicity in 83%, local adhesion in 8% of patients. The group without pericardial changes was distinguished by the presence of epicardial fat >7 mm. A combination of the echo-cardiography criteria with the second symptom recorded at the visit or earlier was present in 76% of the applicants. Comparison of the recorded ultrasound patterns with the time elapsed since infection allowed us to distinguish ultrasound phases: 1) the phase of damage (pattern of initial edema) occurred at 1 week, 2) the phase of edema /exudation (pattern of visible effusion) – at 3 weeks, 3) fibrosis (pattern of pericardial compaction) – at 11 weeks, 4) regression of inflammatory changes (pattern of local fibrin deposition) – on week 22, 5) residual signs of transferred inflammation may be visualized in patients with symptoms 44 weeks after COVID-19. Conclusions. Consideration of the infectious process triggered by SARS-CoV-2, as a systemic inflammation, allows us to interpret the phenomenon of pericardial involvement as a reactive serositis having ultrasound phases. It was possible to trace some patterns of echocardiography at different stages of the infectious and post-infectious period. Clinical data of 76% of patients can be interpreted as pericarditis, changes in 20% – as an increase in echogenicity of the pericardium. © 2022 Russian Electronic Journal of Radiology. All rights reserved.

vasive aspergillosis in patients with COVID-19 in intensive care units: sults of a multicenter study.

Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

ASSOCIATION BETWEEN NEW CORONAVIRUS INFECTION AND FETAL GROWTH RESTRICTION.

Objective: To investigate the laboratory and instrumental characteristics of fetal growth restriction (FGR) secondary to novel coronavirus infection (NCI) to identify pathogenetically relevant predictive markers. Material(s) and Method(s): During the epidemic activity of the NCI Delta strain, 140 high-risk pregnant women were tested at 18-21 weeks and 26-34 weeks of gestation. Retrospectively, taking into account the fact of NCI disease and the exclusion of severe somatic and obstetric comorbidities, 2 groups were formed. Group 1 (n=32) included pregnant women with FGR, without a history of NCI. Group 2 (n=41) included pregnant women with FGR who recovered from NCI by the end of the second and third trimesters. Thirty healthy pregnant women served as the controls. In addition to ultrasound assessment of the fetal placental unit, patients underwent testing for markers of inflammation, endothelial hemostasis dysfunction, decidualization, placental angiogenesis, and pathological insulin resistance. Result(s): Pregnant women with a history of NCI had a higher incidence of FGR (1.3 times;OR 2.41 [95% CI 1.12-5.17]), more severe forms of FGR (2 times;OR 3.27 [95% CI 1.22-8.76]), more severe fetal-placental blood flow abnormalities (3.5-fold;OR 11.07 [95% CI 3.68-33.27]), and oligohydramnios (4.5-fold;OR 8.94 [95% CI 3.65-30.17]). The impact of NCI on the formation of placental insufficiency was expressed by an increase in systemic changes (thrombopoiesis, apoptosis), modulation of local processes (decidualization, placental angiogenesis), and the development of pathological insulin resistance and hyperinsulinemia, an immunopathological process of endotheliocytes. The identification of the most informative markers of FGR due to NCI allowed the development of a predictive index. Conclusion(s): An in-depth study of the impact of NCI on the formation of FGR has important scientific and practical implications for the optimization of FGR prediction, which may help identify appropriate patient management strategies for high-risk pregnant women.Copyright © 2023, Bionika Media Ltd.. All rights reserved.

ASSOCIATION BETWEEN NEW CORONAVIRUS INFECTION AND FETAL GROWTH RESTRICTION.

Objective: To investigate the laboratory and instrumental characteristics of fetal growth restriction (FGR) secondary to novel coronavirus infection (NCI) to identify pathogenetically relevant predictive markers. Material(s) and Method(s): During the epidemic activity of the NCI Delta strain, 140 high-risk pregnant women were tested at 18-21 weeks and 26-34 weeks of gestation. Retrospectively, taking into account the fact of NCI disease and the exclusion of severe somatic and obstetric comorbidities, 2 groups were formed. Group 1 (n=32) included pregnant women with FGR, without a history of NCI. Group 2 (n=41) included pregnant women with FGR who recovered from NCI by the end of the second and third trimesters. Thirty healthy pregnant women served as the controls. In addition to ultrasound assessment of the fetal placental unit, patients underwent testing for markers of inflammation, endothelial hemostasis dysfunction, decidualization, placental angiogenesis, and pathological insulin resistance. Result(s): Pregnant women with a history of NCI had a higher incidence of FGR (1.3 times;OR 2.41 [95% CI 1.12-5.17]), more severe forms of FGR (2 times;OR 3.27 [95% CI 1.22-8.76]), more severe fetal-placental blood flow abnormalities (3.5-fold;OR 11.07 [95% CI 3.68-33.27]), and oligohydramnios (4.5-fold;OR 8.94 [95% CI 3.65-30.17]). The impact of NCI on the formation of placental insufficiency was expressed by an increase in systemic changes (thrombopoiesis, apoptosis), modulation of local processes (decidualization, placental angiogenesis), and the development of pathological insulin resistance and hyperinsulinemia, an immunopathological process of endotheliocytes. The identification of the most informative markers of FGR due to NCI allowed the development of a predictive index. Conclusion(s): An in-depth study of the impact of NCI on the formation of FGR has important scientific and practical implications for the optimization of FGR prediction, which may help identify appropriate patient management strategies for high-risk pregnant women.Copyright © 2023, Bionika Media Ltd.. All rights reserved.

ASSOCIATION BETWEEN NEW CORONAVIRUS INFECTION AND FETAL GROWTH RESTRICTION.

Objective: To investigate the laboratory and instrumental characteristics of fetal growth restriction (FGR) secondary to novel coronavirus infection (NCI) to identify pathogenetically relevant predictive markers. Material(s) and Method(s): During the epidemic activity of the NCI Delta strain, 140 high-risk pregnant women were tested at 18-21 weeks and 26-34 weeks of gestation. Retrospectively, taking into account the fact of NCI disease and the exclusion of severe somatic and obstetric comorbidities, 2 groups were formed. Group 1 (n=32) included pregnant women with FGR, without a history of NCI. Group 2 (n=41) included pregnant women with FGR who recovered from NCI by the end of the second and third trimesters. Thirty healthy pregnant women served as the controls. In addition to ultrasound assessment of the fetal placental unit, patients underwent testing for markers of inflammation, endothelial hemostasis dysfunction, decidualization, placental angiogenesis, and pathological insulin resistance. Result(s): Pregnant women with a history of NCI had a higher incidence of FGR (1.3 times;OR 2.41 [95% CI 1.12-5.17]), more severe forms of FGR (2 times;OR 3.27 [95% CI 1.22-8.76]), more severe fetal-placental blood flow abnormalities (3.5-fold;OR 11.07 [95% CI 3.68-33.27]), and oligohydramnios (4.5-fold;OR 8.94 [95% CI 3.65-30.17]). The impact of NCI on the formation of placental insufficiency was expressed by an increase in systemic changes (thrombopoiesis, apoptosis), modulation of local processes (decidualization, placental angiogenesis), and the development of pathological insulin resistance and hyperinsulinemia, an immunopathological process of endotheliocytes. The identification of the most informative markers of FGR due to NCI allowed the development of a predictive index. Conclusion(s): An in-depth study of the impact of NCI on the formation of FGR has important scientific and practical implications for the optimization of FGR prediction, which may help identify appropriate patient management strategies for high-risk pregnant women.Copyright © 2023, Bionika Media Ltd.. All rights reserved.

Clinical efficacy and safety of convalescent plasma therapy for patients with SARS-CoV-2 infection.

Aim: to evaluate the efficacy and safety of convalescent plasma therapy for patients with severe SARS-CoV-2 infection. Material(s) and Method(s): the study included 64 patients with laboratory-confirmed severe new coronavirus infection. The control group consisted of 58 patients who, in addition to standard therapy, received a transfusion of plasma from donors who had recovered from COVID-19. The effectiveness of immune plasma was assessed by the duration of fever, the level of oxygen (SpO2%) in dynamics, the detection of SARSCoV-2 RNA in nasopharyngeal and oropharyngeal swabs using PCR method in dynamics, as well as by the dynamics of blood tests results. Adverse events (any medically adverse events that occurred after immune plasma transfusion) were recorded as safety criteria. Result(s): patients who received convalescent plasma, showed a significantly shorter period of SARS-CoV-2 replication compared with the control group. The use of immune plasma did not have a statistically significant effect on the duration of the fever, as well as the dynamics of blood oxygenation. Also, there were no significant differences compared with the control group when assessing blood tests parameters. Conclusion(s): The use of COVID-19 convalescent plasma to treat severe COVID-19 did not show significant clinical effect but reduced the period of viral replication. It also showed no unexpected or serious adverse events.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

Clinical efficacy and safety of convalescent plasma therapy for patients with SARS-CoV-2 infection.

Aim: to evaluate the efficacy and safety of convalescent plasma therapy for patients with severe SARS-CoV-2 infection. Material(s) and Method(s): the study included 64 patients with laboratory-confirmed severe new coronavirus infection. The control group consisted of 58 patients who, in addition to standard therapy, received a transfusion of plasma from donors who had recovered from COVID-19. The effectiveness of immune plasma was assessed by the duration of fever, the level of oxygen (SpO2%) in dynamics, the detection of SARSCoV-2 RNA in nasopharyngeal and oropharyngeal swabs using PCR method in dynamics, as well as by the dynamics of blood tests results. Adverse events (any medically adverse events that occurred after immune plasma transfusion) were recorded as safety criteria. Result(s): patients who received convalescent plasma, showed a significantly shorter period of SARS-CoV-2 replication compared with the control group. The use of immune plasma did not have a statistically significant effect on the duration of the fever, as well as the dynamics of blood oxygenation. Also, there were no significant differences compared with the control group when assessing blood tests parameters. Conclusion(s): The use of COVID-19 convalescent plasma to treat severe COVID-19 did not show significant clinical effect but reduced the period of viral replication. It also showed no unexpected or serious adverse events.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

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.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review.

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.

Mucormycosis in patients with COVID-19 in Russia: the results of a prospective multi-center study.

We present the results of a prospective multicenter study of risk factors, etiology, clinical features, and treatment outcomes for mucormycosis in patients with COVID-19 (COVID-M) in the Russian Federation. The study included 60 adult patients with COVID-M. To analyze risk factors for COVID-M, we conducted a case-control study. The control group included 60 adult patients with COVID-19 without mucormycosis. To analyze the clinical manifestations of COVID-M, we created a control group of hematological patients with mucormycosis examined in 2011-2020. In patients with COVID-19, the risk of developing mucormycosis was significantly increased with diabetes mellitus (OR=49) and overweight (OR=4,75), as well as with the use of high (>=100 mg per day for prednisolone) doses of glucocorticosteroids (OR= 4,762), especially >=10 days (OR=25,4). The main localization of mucormycosis in patients with CO-VID-19 was the paranasal sinuses (95%) and the orbit (68%). Involvement of >=2 organs was identified in 70% of patients. The main causative agents of mucormycosis were Rhizopus arrhizus (43%) and unidentified mucormycetes (36%). 90-days overall survival of patients with mucormycosis and COVID-19 - 71%. The stay in the ICU (p=0,01), the use of mechanical ventilation (p=0,0481), the presence of CVC (p=0,049), CNS damage (p=0,016) and >= 2 organs (p=0,048) significantly worsened the prognosis of the disease. The best prognosis was in patients who received antifungal therapy (p=0,03875) and surgical treatment (p=0,046).Copyright © 2022 Authors. All rights reserved.

Mucormycosis in patients with COVID-19 in Russia: the results of a prospective multi-center study

We present the results of a prospective multicenter study of risk factors, etiology, clinical features, and treatment outcomes for mucormycosis in patients with COVID-19 (COVID-M) in the Russian Federation. The study included 60 adult patients with COVID-M. To analyze risk factors for COVID-M, we conducted a case-control study. The control group included 60 adult patients with COVID-19 without mucormycosis. To analyze the clinical manifestations of COVID-M, we created a control group of hematological patients with mucormycosis examined in 2011–2020. In patients with COVID-19, the risk of developing mucormycosis was significantly increased with diabetes mellitus (OR=49) and overweight (OR=4,75), as well as with the use of high (≥100 mg per day for prednisolone) doses of glucocorticosteroids (OR= 4,762), especially ≥10 days (OR=25,4). The main localization of mucormycosis in patients with CO-VID-19 was the paranasal sinuses (95%) and the orbit (68%). Involvement of ≥2 organs was identified in 70% of patients. The main causative agents of mucormycosis were Rhizopus arrhizus (43%) and unidentified mucormycetes (36%). 90-days overall survival of patients with mucormycosis and COVID-19 – 71%. The stay in the ICU (p=0,01), the use of mechanical ventilation (p=0,0481), the presence of CVC (p=0,049), CNS damage (p=0,016) and ≥ 2 organs (p=0,048) significantly worsened the prognosis of the disease. The best prognosis was in patients who received antifungal therapy (p=0,03875) and surgical treatment (p=0,046). © 2022 Authors. All rights reserved.

Mucormycosis in patients with COVID-19 in Russia: the results of a prospective multi-center study.

We present the results of a prospective multicenter study of risk factors, etiology, clinical features, and treatment outcomes for mucormycosis in patients with COVID-19 (COVID-M) in the Russian Federation. The study included 60 adult patients with COVID-M. To analyze risk factors for COVID-M, we conducted a case-control study. The control group included 60 adult patients with COVID-19 without mucormycosis. To analyze the clinical manifestations of COVID-M, we created a control group of hematological patients with mucormycosis examined in 2011-2020. In patients with COVID-19, the risk of developing mucormycosis was significantly increased with diabetes mellitus (OR=49) and overweight (OR=4,75), as well as with the use of high (>=100 mg per day for prednisolone) doses of glucocorticosteroids (OR= 4,762), especially >=10 days (OR=25,4). The main localization of mucormycosis in patients with CO-VID-19 was the paranasal sinuses (95%) and the orbit (68%). Involvement of >=2 organs was identified in 70% of patients. The main causative agents of mucormycosis were Rhizopus arrhizus (43%) and unidentified mucormycetes (36%). 90-days overall survival of patients with mucormycosis and COVID-19 - 71%. The stay in the ICU (p=0,01), the use of mechanical ventilation (p=0,0481), the presence of CVC (p=0,049), CNS damage (p=0,016) and >= 2 organs (p=0,048) significantly worsened the prognosis of the disease. The best prognosis was in patients who received antifungal therapy (p=0,03875) and surgical treatment (p=0,046).Copyright © 2022 Authors. All rights reserved.

Extracorporeal membrane oxygenation for extremely severe new coronavirus infection (COVID-19) in a pregnant woman

The authors report successful veno-venous extracorporeal membrane oxygenation (VV-ECMO) procedure for severe acute respiratory distress syndrome (ARDS) associated with a new coronavirus infection (COVID-19) in a 28-year-old pregnant woman. VV-ECMO was started in 11 days after onset of disease (9 days after caesarean section at 29 weeks of pregnancy for severe pre-eclampsia). Before VV-ECMO procedure, PaCO2 was 50.9 mm Hg, PaO2 68.2 mm Hg, and PaO2 /FiO2 68 under mechanical ventilation with FiO2 100%. Baseline parameters of VV-ECMO were as follows: rotor performance 3200 rpm, volumetric per-fusion rate 4200 ml/min, gas flow 5.5 l/min. After 15 days, the patient was successfully weaned from VV-ECMO. After 5 days, she was transferred to spontaneous breathing. The patient was discharged in 28 days after weaning from VV-ECMO. Apparently, timely VV-ECMO procedure in intensive care of pregnant women with COVID-19 and severe hypoxemic respiratory failure in-creases survival and provides time for lung recovery. © 2023, Media Sphera Publishing Group. All rights reserved.