A Case of X-Linked Moesin-Associated Immune Deficiency in a Pediatric Patient

Background: X-Linked Moesin-Associated Immune Deficiency (X-MAID) is a rare severe combined immunodeficiency (SCID) subtype that can present at any age due to its variability. Depending on severity, patients demonstrate failure to thrive, recurrent bacterial and viral infections, and increased susceptibility to varicella zoster. It has been characterized by marked lymphopenia with hypogammaglobulinemia and impaired T-cell migration and proliferation. Case Presentation: This is a report of a Cuban 7-year-old male with poor weight gain and facial dysmorphia. He had a history of recurrent bacterial gastrointestinal infections and pneumonia beginning at 4 months of age. He additionally had 4-6 upper respiratory tract and ear infections annually. While still living in Cuba, he was admitted for a profound EBV infection in the setting of significant leukopenia. A bone marrow biopsy confirmed no malignancy. After he moved to the United States, his laboratory work-up revealed marked leukopenia with low absolute neutrophil and lymphocyte count with low T and B cells, very low immunoglobulin levels IgG, IgA, and IgM, and poor vaccination responses to streptococcus pneumonia, varicella zoster, and SARS-CoV-2. Genetic testing revealed a missense pathogenic variant c.511C>T (p.Arg171Trp) in the moesin (MSN) gene associated with X-MAID. He was managed with Bactrim and acyclovir prophylaxis, and immunoglobulin replacement therapy, and considered for hematopoietic stem cell transplantation. Discussion(s): Diagnosis of X-MAID should be considered in patients with recurrent infections and profound lymphopenia. As with SCID, early diagnosis and intervention is of utmost importance to prevent morbidity and mortality. This case demonstrates the importance of genetic testing in identifying this disease as it may prompt an immunologist to consider HSCT if conservative management is suboptimal. In the current literature, HSCT appears promising, but the long-term outcomes have yet to be described.Copyright © 2023 Elsevier Inc.

Examining the frequency of endoscopic findings in patients with covid-19 with upper gastrointestinal bleeding referred to al-Zahra Hospital of Isfahan.

Background: Gastrointestinal bleeding is one of the consequences of COVID-19, which is associated with increased hospitalization and patient mortality. This study was conducted to determine the prevalence of endoscopic findings and the outcome of gastrointestinal bleeding in patients with COVID-19 who were hospitalized from September to December 2019 in Al-Zahra Hospital, Isfahan. Method(s): In this cross-sectional study, out of 5800 patients who were admitted to Al-Zahra Hospital in Isfahan from September to December 2019 due to COVID-19 (according to the positive PCR test result), 87 patients who underwent endoscopy due to upper gastrointestinal bleeding by a skilled gastroenterologist, were selected and studied. Demographic characteristics, underlying diseases, use of anticoagulants, and laboratory findings were studied and evaluated and finally, the disease was evaluated and compared based on endoscopic findings. Result(s): Based on the results obtained from this research, the patients with endoscopic lesions had higher average age (P=0.041), lower blood oxygen saturation percentage (P=0.028), and higher bleeding intensity (P=0.018). The frequency of using anticoagulant drugs in the group whose endoscopy results were abnormal was higher but insignificant. Hemoglobin, platelet, lymphocyte, and CRP levels were higher in the group whose endoscopy was normal, and NLR, LDH, and D-dimer levels were higher in the group whose endoscopy was abnormal (P<0.050). Three people (11.55%) from the group with normal endoscopy and 18 people (29.5%) from the group with abnormal endoscopy died, but the frequency of death was not significantly different between the two groups (P=0.070). Conclusion(s): The findings of the present study showed that the COVID patients with upper gastrointestinal bleeding who had endoscopic lesions had significant differences in some characteristics such as age, bleeding intensity, and blood oxygen saturation percentage with patients with normal endoscopy. Also, the frequency of death in patients with endoscopic lesions was relatively higher. Therefore, COVID patients with gastrointestinal bleeding should undergo endoscopy as soon as possible and necessary measures should be taken to control and prevent gastrointestinal bleeding.Copyright © 2022 Tabesh et al. Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.

Mild COVID-19 clinical course among paediatric patients with primary immunodeficiency

Background: The clinical course of coronavirus disease-2019 (COVID-19) varies from those who are asymptomatic, experience mild symptoms such as fever, cough, and dyspnea, to more severe outcomes including acute respiratory distress, pneumonia, renal failure, and death. Early reports suggested severe outcomes in patients with primary immunodeficiency (PID), particularly those with type 1 interferon signalling defects. This prompted a rigid approach to social distancing to protect this patient population, particularly children. To date, real-world data describing the course and outcome of COVID-19 in paediatric PID patients remains scarce. Method(s): In this retrospective case series, we describe the clinical course of 36 paediatric patients with underlying primary immunodeficiency (PID) followed by SickKids Hospital (Toronto, Canada) who were symptomatic and tested positive for SARS-CoV-2 infection between October 2020 to November 2022. Result(s): Our cohort consisted of patients with combined immunodeficiency (66.7%), antibody deficiency (22.2%), neutrophil dysfunction (8.3%), and immune dysregulation (2.8%). The median age was 7.5 years (range: 8 months - 17 years), with 21 male and 15 female patients. Three (8.3%) patients were post-hematopoietic stem cell transplant (HSCT) and 12 (33%) patients were on immunoglobulin replacement. Nine (25%) patients had underlying lung problems including bronchiectasis (1), interstitial lung disease on home oxygen therapy (1), and underlying asthma (7). Most patients had mild clinical course and were managed at home. The most common symptoms were fever (80%), cough (75%) and other upper respiratory tract symptoms (72%). Nineteen (52.7%) patients experienced other symptoms which included headache, lethargy, or gastrointestinal upset. At the time of the infection, 13 patients (36.1%) had received 2 doses of a SARS-CoV-2 vaccine, 5 patients (13.9%) had received 1 dose, and 18 (50%) were not vaccinated. None of the patients received antiviral or monoclonal antibody as prophylaxis or treatment. Only 1 patient required hospital admission out of precaution given the close proximity to HSCT. All patients recovered without complications. Conclusion(s): The paediatric patients with PID followed by our centre experienced mild to moderate COVID-19 symptoms and recovered fully without complications. These findings support the return of much needed social interactions among children, which were impacted severely during the COVID-19 pandemic.Copyright © 2023 Elsevier Inc.

Clinical and laboratory indicators in predicting the risk of chronic heart failure in COVID-19 survivors.

Coronavirus disease has many systemic disease symptoms and has severe consequences for the cardiovascular system. Objective. To assess the role of clinical and laboratory indicators in determining the risk of chronic heart failure (CHF) in COV-ID-19 survivors. Material and methods. In total, 151 patients treated in a monoinfectious hospital from 03.11.20 to 10.02.21 with a confirmed diagnosis of COVID-19 were retrospectively selected. Medical history and laboratory data were collected by reviewing electronic medical records. The data included age, gender, body mass index, smoking status, and comorbidities. The laboratory data included the results of hematology and blood chemistry, coagulation, and the levels of acute-phase proteins. The CHF occurrence was used as the study endpoint. Results and discussion. The study patients were divided into two groups depending on the presence of CHF: group 1 included 46 patients with CHF, and group 2 included 105 patients without CHF. The median age was 66.2 (50-92) years;91 (60.3%) were females. Laboratory tests, such as levels of the hs-C-reactive protein, lactate dehydrogenase, procalcitonin, creatinine, and bilirubin, were statistically significantly different in patients of the study groups, and the median values were higher in patients with CHF. Neutrophil-lymphocyte ratio (NLR) showed statistically significant differences between groups: in patients with CHF, the median was 4.97% compared to 3.62% (p=0.011) in those without CHF. The most significant predictors of an increased risk of CHF were age >=66 years (OR=8.038, p<0.001), procalcitonin level >=0.09 ng/mL (increased the CHF risk by 3.8 times, p<0.001), thrombocy-topenia <=220x109/L (p=0.010), an NLR ratio >=4.11% (p=0.010), and a history of chronic kidney disease (p=0.018). Conclusion. A model has been developed to determine the factors closely associated with the risk of chronic heart failure in CO-VID-19 survivors.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

Direct bilirubin and the neutrophil-to-monocyte ratio timely predict intensive care unit admission in patients with severe acute respiratory syndrome coronavirus-2 infection (COVID-19)

Objective: Intensive care units (ICUs) collapsed under the global wave of coronavirus disease 2019 (COVID-19). Thus, we designed a clinical decision-making model that can help predict at hospital admission what patients with COVID-19 are at higher risk of requiring critical care. Method(s): This was a cross-sectional study in 119 patients that met hospitalization criteria for COVID-19 including less than 30 breaths per minute, peripheral oxygen saturation < 93%, and/or >= 50% lung involvement on imaging. Depending on the need for critical care, patients were retrospectively assigned to ICU and non-ICU groups. Demographic, clinical, and laboratory parameters were collected at admission and analyzed by classification and regression tree (CRT). Result(s): Forty-five patients were admitted to ICU and 80% of them were men older than 57.13 +/- 12.80 years on average. The leading comorbidity in ICU patients was hypertension. The CRT revealed that direct bilirubin (DB) > 0.315 mg/dl together with the neutrophil-to-monocyte ratio (NMR) > 15.90 predicted up to correctly in 92% of the patients the requirement of intensive care management, with sensitivity of 93.2%. Preexisting comorbidities did not influence on the tree growing. Conclusion(s): At hospital admission, DB and NMR can help identify nine in 10 patients with COVID-19 at higher risk of ICU admission.Copyright © 2022 Sociedad Medica del Hospital General de Mexico.

Liver biomarkers for prognosis in COVID-19

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).Mortality attributable to COVID-19 remains considerably high, with case fatality rates as high as 8-11%. Early medical intervention in patients who are seriously and critically ill with COVID-19 reduces fatal outcomes. Thus, there is an urgent need to identify biomarkers that could help clinicians determine which patients with SARS-CoV-2 infection are at a higher risk of developing the most adverse outcomes, which include intensive care unit (ICU) admission, invasive ventilation, and death. In COVID-19 patients experiencing the most severe form of the disease, tests of liver function are frequently abnormal and liver enzymes are found to be elevated. For this reason, we examine the most promising liver biomarkers for COVID-19 prognosis in an effort to help clinicians predict the risk of ARDS, ICU admission, and death at hospital admission. In patients meeting hospitalization criteria for COVID-19, serum albumin < 36 g/L is an independent risk factor for ICU admission, with an AUC of 0.989, whereas lactate dehydrogenase (LDH) values > 365 U/L accurately predict death with an AUC of 0.943.The clinical scores COVID-GRAM and SOFA that include measures of liver function such as albumin, LDH, and total bilirubin are also good predictors of pneumonia development, ICU admission, and death, with AUC values ranging from 0.88 to 0.978.Thus, serum albumin and LDH, together with clinical risk scores such as COVID-GRAM and SOFA, are the most accurate biomarkers in the prognosis of COVID-19.Copyright © 2021 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.

Tocilizumab Initiation based on Indicator in Patients Infected by Coronavirus-19 to Prevent Intubation

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has created severe medical and economic consequences worldwide since 2019. Tocilizumab is one of the therapies considered capable of improving the condition of patients with COVID-19. However, there is not much information about the best time to give tocilizumab. METHOD(S): This was an analytical study with a retrospective cohort design, using the data of 125 patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with signs of acute respiratory distress syndrome in Dr. Moewardi Hospital, Surakarta, from March to August 2020. We analyzed various available clinical data to see which factors into clinical improvement with tocilizumab therapy. RESULT(S): Most patients showed clinical improvement after administration of tocilizumab. During the follow-up period, 21 patients died despite tocilizumab therapy. Significant risk factors associated with the need for intubation were heart rate, neutrophil, lymphocyte, pH, PaCO2, and PO2. The most influential variable on the need for intubation without being associated with other risk factors was PaO2 (p = 0.003, Confidence Intervals 95%). CONCLUSION(S): Tocilizumab has a role in treating patients infected by SARS-CoV-2, preventing the need for intubation when given to patients in good saturation condition with oxygen supplementation without positive pressure (PaO2 >65mmHg;SpO2 >93%).Copyright © 2023 Septian Adi Permana, Adhrie Sugiarto, Sidharta Kusuma Manggala, Muhammad Husni Thamrin, Purwoko Purwoko, Handayu Ganitafuri.

Controversial role of neutrophilic granulocytes in the immunopathogenesis of COVID-19: correlation with imbalance of pro-inflammatory neutrophil-associated cytokines and interferon alpha deficiency.

Neutrophilic granulocytes (NG) are the main drivers of pathological inflammation in COVID-19. Objective. To specify the mechanisms of immunopathogenesis of COVID-19 based on a comparative immunological study of the number and phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets with an assessment of their effector functions against changing profile of NG-associated cytokines IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma. Patients and methods. In patients with moderate-to-severe and severe COVID-19, we determined IL-1beta, TNFalpha, IL-6, IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma (ELISA), the phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets, NF-kappaB-NG (CYTOMICS FC500), phagocytically active NG (%), neutrophil extracellular traps (NETs), NG in apoptosis, and the activity of NADPH oxidase. Results. In COVID-19 against the background of IFNalpha and IFNgamma production blockade and high levels of NG-associated IL-8, IL-18, IL-17A, VEGF-A, a reduction in the number of mature and functionally active CD16brightSD62LbrightCD11bbrightCD63-NG subsets was revealed, as well as an increase in the number of CD16dimSD62LdimSD11bbrightCD63-NG subsets with an immunosuppressive phenotype and CD16brightSD62LbrightSD11bbrightCD63bright-NG subsets with high cytotoxic activity and ability to form NETs, a decrease in the percentage of phagocytically active NG and an increase in the activity of NADPH oxidase, NETs, and NG in apoptosis. Conclusion. IFNalpha deficiency provokes a hyperergic response of NG-associated cytokines, which leads to the formation of uncontrolled immune inflammation involving NG subsets with an immunosuppressive and cytotoxic phenotype, exacerbating the course of COVID-19. The use of recombinant IFNalpha-2b with antioxidants (Viferon) in the early stages of the disease can help to restore immune homeostasis, normalize the level of NG-associated cytokines, reduce NERTs, and achieve good clinical efficacy.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Mesenchymal Stem/Stromal Cells: DEVELOPMENT OF A GMP BANKING PROCESS FOR UMBILICAL CORD MESENCHYMAL STROMAL CELLS (UC-MSCS) AND USE OF UC-MSC IN CHARACTERISATION ASSAYS, FUNCTIONAL ASSAYS AND GENE EDITING STUDIES

Background & Aim: The pro-angiogenic, immunoregulatory and anti- inflammatory properties of MSCs are being exploited for the development of cellular therapies, including the treatment of graft versus host disease (GvHD), inflammatory bowel disease and COVID-19. SNBTS have developed a GMP process to bank umbilical cord MSCs (UC-MSCs) whereby we can reliably bank 100 vials of 10 million P2 UC-MSCs per cord. Each of these vials can be extensively expanded and stored for specific applications. The ultimate aim of the bank is for off-the-shelf clinical use, e.g., in GvHD or as an adjuvant therapy in Islet transplantations. Methods, Results & Conclusion(s): During process development, different basal media and supplements were screened for proliferation and MSC marker expression. Cells grown in promising media combinations were then tested for tri-lineage differentiation (identity), their chemokine/cytokine expression and T-cell inhibition (function) assessed. Medium selected for further GMP development and scale up was ultimately determined by all round performance and regulatory compliance. GMP-like UC-MSCs were shown to have immune-modulatory activity in T-cell proliferation assays at 4:1 or 16:1 ratios. Co-culture of UC-MSCs and freshly isolated leukocytes, +/- the immune activating agent LPS, show a dose dependent survival effect on leukocytes. In particular, neutrophils, which are normally very short lived in vitro demonstrated increased viability when co-cultured with UCMSCs. The survival effect was partially reproduced when UC-MSC were replaced with conditioned medium or cell lysate indicating the involvement of soluble factors. This improved neutrophil survival also correlates with results from leukocyte migration studies that demonstrate neutrophils to be the main cell type attracted to MSCs in in vitro and in vivo. Genetic modification of UC-MSC may improve their therapeutic potential. We have tested gene editing by CRISPR/Cas9 technology in primary UC-MSCS. The CXCL8 gene, highly expressed in UC-MSC, was targeted in isolates from several different donors with editing efficiencies of 78-96% observed. This translated to significant knockdown of CXCL8 protein levels in resting cells, however after stimulation levels of CXCL8 were found to be very similar in edited and non-edited UC-MSCs. This observation requires further study, but overall the results show the potential to generate future banks of primary UC-MSCS with genetically enhanced pro-angiogenic, immunoregulatory and/or anti-inflammatory activities.Copyright © 2023 International Society for Cell & Gene Therapy

Liver dysfunction as a respiratory prognostic factor in covid-19 patients.

Respiratory dysfunction is a main clinical symptom of COVID-19. Liver dysfunction is also frequently reported in patients with COVID-19 and considered to be related to a poor prognosis. However, the precise mechanisms behind these findings remain unclear. We investigated the clinical features and prognostic factors related to liver dysfunction in 26 COVID-19 pa-tients. The patients with liver dysfunction had markedly higher WBC, neutrophils, CRP, and frequency of oxygen administration and markedly lower PaO2/FIO2 ratios. The patients with liver dysfunction had longer mean hospital stays. In conclusion, liver dysfunction at hospital admission may be an important prognostic factor for respiratory failure in patients with COVID-19. We must administer intensive care to these patients earlier to inhibit severe disease progression.Copyright ©2021 The Japan Society of Hepatology.

Clinical and laboratory markers of severity of the new coronavirus infection (COVID-19).

The aim of the research. To study clinical and laboratory features of the new coronavirus infection (COVID-19) in order to develop a model that would allow, taking the publicly available research methods into account, to carry out early diagnosis of severe community-acquired pneumonia against the background of the new coronavirus infection. Material and methods. A total of 82 COVID-19 patients who complied with inclusion and exclusion criteria were enrolled. Depending on the clinical severity, three study groups were formed: group 1 included 13 patients with uncomplicated COVID-19, group 2 consisted of 39 patients with non-severe forms of pneumonia that developed against COVID-19 and group 3 was comprised of 30 patients with COVID-19 complicated by severe pneumonia. The groups were comparable in age and gender. All patients underwent general clinical examination, laboratory tests, including general and biochemical blood analysis, as well as chest computed tomography. Results. The clinical picture in COVID-19 patients differed depending on the disease severity. Coughing and shortness of breath were more often observed in patients with severe pneumonia;sore throat, on the contrary, was more often noted in patients with uncomplicated COVID-19. On admission to the inpatient facility, patients with severe pneumonia had higher body temperature and respiratory rate, with simultaneous decrease in blood oxygen saturation. One half of the patients with severe pneumonia had hypertensive disease in medical history, and one third had ischaemic heart disease. As a rule, uncomplicated COVID-19 patients did not have ischaemic heart disease. It was found through laboratory analysis of blood that groups of patients significantly differed in the levels of neutrophils, lymphocytes, monocytes, basophils and eosinophils. Conclusion. The use of such clinical and laboratory data as acute respiratory failure, fever, the levels of neutrophils, monocytes, lymphocytes, eosinophils and basophils makes it possible to identify patients with more severe pneumonia against the background of COVID-19 even before chest computed tomography. Key words:.Copyright © 2022, Krasnoyarsk State Medical University. All rights reserved.

The Association of COVID-19 Severity with Laboratory Parameters, Radiologic Findings, Maternal and Neonatal Outcomes in Pregnant Women: A Multicenter Study in Indonesia

Objectives: Severe acute respiratory syndrome-coronavirus 2/COVID-19 infection is still a global concern, with pregnant women are considered as vulnerable population. Until now, the characteristics of pregnant women in Indonesia who are infected with COVID-19, as well as pregnancy and neonatal outcomes, are still unknown. This study aims to obtain national data, which are expected to be useful for the prevention and management of COVID-19 in pregnant women in Indonesia. Method(s): There were 1,427 patients recruited in this retrospective multicenter study. This study involved 11 hospitals in 10 provinces in Indonesia and was carried out using secondary patient data from April 2020 to July 2021. COVID-19 severity was differentiated into asymptomatic-to-mild symptoms and moderate-to-severe symptoms. The collected data include maternal characteristics, laboratory examinations, imaging, pregnancy outcomes, and neonatal outcomes. Result(s): Leukocyte, platelets, basophil, neutrophils segment, lymphocytes, monocytes, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), urea, and creatinine were found to be significantly associated with severity differences (p < 0.05). Moderate-severe symptoms of COVID-19 also shown to have suggestive pneumonia findings on chest X-ray findings. Patients with asymptomatic-to-mild symptoms had significantly (p < 0.001) higher recovery rate, shorter hospital stay, less intensive care unit (ICU) admission, and had more vaginal delivery. Neonates from mother with mild symptoms also had significantly (p < 0.001) higher survival rate, higher birth weight, and higher APGAR score. Conclusion(s): Several laboratory and radiology components, as well as maternal and neonatal outcomes are related to the severity of COVID-19 in pregnant women in Indonesia.Copyright © The Author(s). 2023.

Association between Type 2 Diabetes Mellitus and Covid-19 Severity: A Literature Review

We conducted a review and evaluated the already documents reports for the relationship among diabetes and COVID-19. The review outcome shows that the COVID-19 severity seems to be greater among patients with diabetes as comorbidity. So, strict glycemic control is imperative in patients infected with COVID-19. Thus, world-wide diabetes burden and COVID-19 pandemic must be deliberated as diabetes increases the COVID-19 severity. Established on this, it is precise significant to follow specific treatment protocols and clinical management in COVID-19 patients affected with diabetes to prevent morbidity and mortality.Copyright © 2023 The Authors.

2C5-surface modified nanocarriers targeting neutrophil extracellular traps

Background: Neutrophil extracellular traps (NETs) are composed of processed chromatin bound to granular and selected cytoplasmic proteins and released by neutrophils. NETs consist of smooth filaments composed of stacked nucleosomes. Fully hydrated NETs have a cloud-like appearance and occupy a space 10-15-fold larger than the volume of the cells they originate from. DNases are the enzymes that cleave extracellular DNA including NETs. Together with their protective role in microbial infections, NETs are involved in multiple pathological processes and represent key events in a variety of pathologies including cancer, autoimmunity, and cardiovascular disease. Sites of NETs concentration are dangerous for the host if the process of NETs formation becomes chronic or the mechanism of NETs removal does not work. NETosis has been linked to the development of periodontitis, cystic fibrosis, type 2 diabetes, COVID-19 or rheumatoid arthritis as well as cancer progression. Purpose(s): Thus, the destruction of NETs is of primary significance in many pathologies. In our approach, we are focusing on mimicking one of the natural mechanisms of destroying excessive NETs by delivering deoxyribonuclease I to the specific site of pathological NETs accumulation by modifying the nanoparticles using an anti-nucleosome monoclonal antibody (2C5). The antibody is specific to nucleosomes and can recognize histones in NETs. DNase I is U.S. Food and Drug Administration (FDA)-approved active component and is commonly used in therapeutic methods of modern medicine for cystic fibrosis to clear extracellular DNA fibers in the lungs and systemic lupus erythematosus. Recent findings have also shown the effectiveness of DNase I in the digestion of NETs. However, the low serum stability and fast deactivation by environmental stimuli have been considered as the limiting factors for clinical applications of DNase I, which can be overcome by its targeted specific delivery in pharmaceutical nanocarriers. Method(s): In this study, we generate NETs in vitro using human neutrophils and HL-60 cells differentiated into granulocyte-like cells. We used interleukin-8, lipopolysaccharide from E.Coli (LPS), phorbol myristate acetate (PMA), and calcium ionophore A23187 (CI) to generate the NETs. We confirmed the specificity of 2C5 toward NETs by ELISA, which showed that it binds to NETs with the specificity like that for purified nucleohistone substrate. We further utilized that feature to create two delivery systems (liposomes and micelles) for DNAse I enzyme to destroy NETs, which was confirmed by staining NETs with SYTOX Green dye and followed by flow cytometric measurements and microscopic images. Conclusion(s): Our results suggest that 2C5 could be used to identify and visualize NETs and serve as a ligand for NET-targeted diagnostics and therapies. Also, we proved that our carrier can successfully deliver DNase to NETs to provide their degradation.

Predictors of Mortality in Sepsis Patients Resulting from Severe and Critical COVID-19

Patients with severe and critical COVID-19 may exhibit sepsis and mortality resulting from multi-organ failure. Neutrophil-lymphocyte-ratio (NLR) values, C-reactive protein (CRP) levels, sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHE-II) scores were used to assess the risk of mortality in sepsis patients resulting from severe COVID-19 infection. The adequacy of NLR, CRP, SOFA, and APACHE-II scores were evaluated as predictors of mortality in septic COVID-19 patients at Dr. Kariadi Hospital Semarang, Indonesia, between August 2021 and July 2022. The subjects included severe and critical COVID-19 patients who fulfilled the WHO interim guidelines and Sepsis-3 criteria. A total of 211 patients were included, which were divided into survivor (n = 116) and non-survivor (n = 95) groups. NLR values, CRP levels, SOFA, and APACHE-II scores were measured within 24 hours of patient admission. Univariate and multivariate logistic regression analyses were used to identify the risk factors for COVID-19 mortality. Receiver operating characteristic curve analysis was used to predict the mortality of severe COVID-19 patients. The results indicated that the APACHE-II score was an independent predictor of mortality in sepsis patients resulting from severe and critical COVID-19. © 2023 by SPC (Sami Publishing Company).

Acute Coronary Syndrome during the Pandemic New Coronavirus Infection.

The experience of managing patients with COVID-19 around the world has shown that, although respiratory symptoms predominate during the manifestation of infection, then many patients can develop serious damage to the cardiovascular system. However, coronary artery disease (CHD) remains the leading cause of death worldwide. The purpose of the review is to clarify the possible pathogenetic links between COVID-19 and acute coronary syndrome (ACS), taking into account which will help to optimize the management of patients with comorbid pathology. Among the body's responses to SARS-CoV-2 infection, which increase the likelihood of developing ACS, the role of systemic inflammation, the quintessence of which is a "cytokine storm" that can destabilize an atherosclerotic plaque is discussed. Coagulopathy, typical for patients with Covid-19, is based on immunothrombosis, caused by a complex interaction between neutrophilic extracellular traps and von Willebrandt factor in conditions of systemic inflammation. The implementation of a modern strategy for managing patients with ACS, focused on the priority of percutaneous interventions (PCI), during a pandemic is experiencing great difficulties due to the formation of time delays before the start of invasive procedures due to the epidemiological situation. Despite this, the current European, American and Russian recommendations for the management of infected patients with ACS confirm the inviolability of the position of PCI as the first choice for treating patients with ACS and the undesirability of replacing invasive treatment with thrombolysis.Copyright © 2023 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.

Pulmonary influenza infection promotes the awakening of dormant metastatic breast cancer cells

Breast cancer is the most common form of cancer and the second cancer-causing death in females. Although remission rates are high if detected early, survival rates drop substantially when breast cancer becomes metastatic. The most common sites of metastatic breast cancer are bone, liver and lung. Respiratory viral infections inflict illnesses on countless people. The latest pandemic caused by the respiratory virus, SARS-CoV-2, has infected more than 600 million worldwide, with documented COVID-related death upward of 1 million in the United States alone. Respiratory viral infections result in increased inflammation with immune cell influx and expansion to facilitate viral clearance. Prior studies have shown that inflammation, including through neutrophils, can contribute to dormant cancer cells reawakening and outgrowth. Moreover, inhibition of IL6 has been shown to decrease breast cancer lung metastasis in mouse models. However, how respiratory viral infections contribute to breast cancer lung metastasis remains to be unraveled. Using MMTV/PyMT and MMTV/NEU mouse models of breast cancer lung metastasis and influenza A virus as a model respiratory virus, we demonstrated that acute influenza infection and the accompanying inflammation and immune cell influx awakens and dramatically increased proliferation and expansion of dormant disseminated cancer cells (DCC) in the lungs. Acute influenza infection leads to immune influx and expansion, including neutrophils and macrophages, with increased proportion of MHCII+ macrophages in early time points, and a sustained decrease in CD206+ macrophages starting 6 days post-infection until 28 days after the initial infection. Additionally, we observed a sustained accumulation of CD4+ T cells around expanding tumor cells for as long as 28 days after the infection. Notably, neutrophil depletion or IL6 knockout reversed the flu-induced dormant cell expansion in the lung. Finally, awakened DCC exhibited downregulation of vimentin immunoreactivity, suggesting a role for phenotypic plasticity in DCC outgrowth following viral infection. In conclusion, we show that respiratory viral infections awaken and increase proliferation of dormant breast cancer cells in the lung, and that depletion of neutrophils or blocking IL6 reverses influenza-induced dormant cell awakening and proliferation.

Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India

Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objective(s): This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Material(s) and Method(s): This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Result(s): A total of 650 tests for COVID-19 were performed for 181 children;22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support;all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusion(s): Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.

Clinical characteristics and risk factors of patients with COVID-19 developing barotrauma

Background: At our hospital, people with COVID-19 (coronavirus disease 2019) had a high rate of pulmonary barotrauma. Therefore, the current study looked at barotrauma in COVID-19 patients getting invasive and non-invasive positive pressure ventilation to assess its prevalence, clinical results, and features. Methodology: Our retrospective cohort study comprised of adult COVID-19 pneumonia patients who visited our tertiary care hospital between April 2020 and September 2021 and developed barotrauma. Result(s): Sixty-eight patients were included in this study. Subcutaneous emphysema was the most frequent type of barotrauma, reported at 67.6%;pneumomediastinum, reported at 61.8%;pneumothorax, reported at 47.1%. The most frequent device associated with barotrauma was CPAP (51.5%). Among the 68 patients, 27.9% were discharged without supplemental oxygen, while 4.4% were discharged on oxygen. 76.5% of the patients expired because of COVID pneumonia and its complications. In addition, 38.2% of the patients required invasive mechanical breathing, and 77.9% of the patients were admitted to the ICU. Conclusion(s): Barotrauma in COVID-19 can pose a serious risk factor leading to mortality. Also, using CPAP was linked to a higher risk of barotrauma.Copyright © 2021 Muslim OT et al.

EXPERIENCE WITH TIXAGEVIMAB AND CILGAVIMAB (EVUSHELD) IN 86 RHEUMATIC PATIENTS UNDERGOING ANTI-B CELL THERAPY WITH RITUXIMAB.

The problem of prevention of coronavirus disease 2019 (COVID-19) in patients with immune-mediated inflammatory rheumatic diseases (IMRD) remains highly relevant. The presence of IRD is associated with a high risk of disease and severe course of COVID-19 during immunosuppressive treatment, primarily anti-B cell therapy with rituximab (RTX), and a low level of post-vaccination response in such patients. A new strategy for the prevention and treatment of COVID-19 are virus-neutralizing monoclonal antibodies to coronavirus;currently, combined long-acting monoclonal antibodies tixagevimab and cilgavimab (Evusheld) are registered for prevention in the world and the Russian Federation. . Tixagevimab and cilgavimab (TC) show neutralizing activity against SARS-CoV-2, including the Omicron strain, primarily its variants BA.4, BA.5, BA.2.75 ("Centaur"). Objective - to evaluate the efficacy and safety of TC for pre-exposure prophylaxis of COVID-19 in rheumatic patients receiving RTX, based on a prospective observational study. Materials and methods. The main group included 86 patients with various IMRD receiving RTX: 50 of them had ANCA-associated systemic vasculitis (AAV), 15 - rheumatoid arthritis, 9 - Sjogren's syndrome (SS), 4 - IgG4-related disease, 3 - systemic lupus erythematosus (SLE), 3 - dermatomyositis (DM), 2 - systemic scleroderma (SSD). Median age was 59 (19-82) years;male: female ratio - 1:1,8. From March 26 to August 30 2022, patients received a single intramuscular injection of TC in a total dose of 300 mg, mainly after RTX (in 52% of cases, in 28% on the next day after RTX). The control group included 42 patients with AAV (median age - 45 (35-71) years;male: female ratio - 1:1), also treated with RTX, who did not receive pre-exposure prophylaxis of TC. The duration of observation was 7 months, until November 1 2022. At this time, 98% of confirmed cases of coronavirus in the Russian Federation were Omicron. A telephone and/or online survey of patient has been conducted to detect cases of COVID-19 and adverse reactions. Results. In the TC group, confirmed coronavirus infection have been detected in 17 (20%) patients (AAV - 10, SS - 3, SSD - 2, SLE - 1, DM - 1), with fever in 7 (8%), only in one case hospitalization was required (lung damage was not detected in computed tomography), in two cases, according to CT mild lung damage (CT 1-2), there were no deaths. Good TC's tolerability was noted, signs not associated with COVID-19 or progression of IMRD after administration of TC were observed in 8 (9%) patients (GPA - 3 MPA - 1, RA - 2, SLE - 1, IgG4-related disease - 1), adverse reactions definitely associated with the use of TC were not found. The most serious event not associated with coronavirus infection was the progression of polyneuropathy in a patient with RA. In the control group, 3 (7%) patients were diagnosed with COVID-19, one with severe lung injury (CT 3, pulmonary embolism) and death. Conclusions. The data of clinical studies and our own clinical experience evidence the effectiveness of the use of a combination of long-acting monoclonal antibodies TC (Evusheld), registered for indications for pre-exposure prophylaxis and treatment of COVID-19. Patients with IMRD treated with RTX have a favorable safety profile of TC. The introduction of virus-neutralizing monoclonal antibodies, a new drug class for the prevention and treatment of infectious diseases, opens significant prospects for improving the prognosis of patients with IRD.Copyright © 2023 Ima-Press Publishing House. All rights reserved.