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1.
Mod Rheumatol Case Rep ; 2021 Sep 04.
Article in English | MEDLINE | ID: covidwho-20239413

ABSTRACT

Coronavirus disease 2019 (COVID-19) possesses a substantial challenge for rheumatologists and rheumatologic patients. They are concerned about the reciprocal interaction between connective tissue diseases, such as systemic lupus erythematosus (SLE), and the virus. Here, we report a 21-year-old female SLE patient presented to the emergency department with gastrointestinal symptoms and kidney involvement evidence. Based on the pathology and laboratory assessments, she was suspected of C-anti-neutrophil cytoplasmic antibody (ANCA) positive SLE and ANCA-associated vasculitis overlap syndrome (SLE/AAV OS), and plasmapheresis every other day was performed due to this diagnosis alongside the high titer of C-ANCA. We also administered methylprednisolone (1 g/day, IV) for three days, followed by dexamethasone with the maintenance dosage (1mg/kg/day, IV). Although the patient's general condition improved the next days, her condition deteriorated suddenly on the 7th day of hospitalization. She got intubated and went to the intensive care unit. Despite taking possible measures to manage the patient's condition, she eventually passed away due to severe acute respiratory distress syndrome (ARDS), triggered by COVID-19. The distinct role of C-ANCA in SLE/AAV vascular damage and activating neutrophil cytokine release accompanied by the impaired immune system while facing COVID-19 seems to lead to increased morbidity and mortality in such patients. This report was presented to bring into consideration the possible role of C-ANCA in the burden and prognosis of COVID-19 in SLE/AAV OS patients.

2.
Front Immunol ; 14: 1170603, 2023.
Article in English | MEDLINE | ID: covidwho-20237245

ABSTRACT

Neutrophil Extracellular Traps (NETs) are a key form of pro-inflammatory cell death of neutrophils characterized by the extrusion of extracellular webs of DNA containing bactericidal killing enzymes. NETosis is heavily implicated as a key driver of host damage in autoimmune diseases where injurious release of proinflammatory enzymes damage surrounding tissue and releases 70 known autoantigens. Recent evidence shows that both neutrophils and NETosis have a role to play in carcinogenesis, both indirectly through triggering DNA damage through inflammation, and directly contributing to a pro-tumorigenic tumor microenvironment. In this mini-review, we summarize the current knowledge of the various mechanisms of interaction and influence between neutrophils, with particular attention to NETosis, and cancer cells. We will also highlight the potential avenues thus far explored where we can intercept these processes, with the aim of identifying promising prospective targets in cancer treatment to be explored in further studies.


Subject(s)
Autoimmune Diseases , Extracellular Traps , Humans , Neutrophils , Inflammation/metabolism , Cell Death
3.
Front Immunol ; 14: 1186000, 2023.
Article in English | MEDLINE | ID: covidwho-20236819

ABSTRACT

Coronavirus disease 2019 (COVID-19) is known to commonly induce a thrombotic diathesis, particularly in severely affected individuals. So far, this COVID-19-associated coagulopathy (CAC) has been partially explained by hyperactivated platelets as well as by the prothrombotic effects of neutrophil extracellular traps (NETs) released from neutrophils. However, precise insight into the bidirectional relationship between platelets and neutrophils in the pathophysiology of CAC still lags behind. Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare autoimmune disorder caused by auto-antibody formation in response to immunization with adenoviral vector vaccines. VITT is associated with life-threatening thromboembolic events and thus, high fatality rates. Our concept of the thrombophilia observed in VITT is relatively new, hence a better understanding could help in the management of such patients with the potential to also prevent VITT. In this review we aim to summarize the current knowledge on platelet-neutrophil interplay in COVID-19 and VITT.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , Humans , Blood Platelets , Neutrophils , COVID-19/complications , Thrombocytopenia/chemically induced , Thrombosis/etiology , Rare Diseases
4.
Biomolecules ; 13(5)2023 04 25.
Article in English | MEDLINE | ID: covidwho-20233944

ABSTRACT

Neutrophils are the most abundant leukocyte in circulation and are the first line of defense after an infection or injury. Neutrophils have a broad spectrum of functions, including phagocytosis of microorganisms, the release of pro-inflammatory cytokines and chemokines, oxidative burst, and the formation of neutrophil extracellular traps. Traditionally, neutrophils were thought to be most important for acute inflammatory responses, with a short half-life and a more static response to infections and injury. However, this view has changed in recent years showing neutrophil heterogeneity and dynamics, indicating a much more regulated and flexible response. Here we will discuss the role of neutrophils in aging and neurological disorders; specifically, we focus on recent data indicating the impact of neutrophils in chronic inflammatory processes and their contribution to neurological diseases. Lastly, we aim to conclude that reactive neutrophils directly contribute to increased vascular inflammation and age-related diseases.


Subject(s)
Extracellular Traps , Nervous System Diseases , Humans , Neutrophils , Cytokines , Phagocytosis , Inflammation
5.
Tehran University Medical Journal ; 80(9):729-736, 2022.
Article in Persian | EMBASE | ID: covidwho-20243535

ABSTRACT

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.

6.
Clinical Immunology ; Conference: 2023 Clinical Immunology Society Annual Meeting: Immune Deficiency and Dysregulation North American Conference. St. Louis United States. 250(Supplement) (no pagination), 2023.
Article in English | EMBASE | ID: covidwho-20242741

ABSTRACT

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.

7.
Profilakticheskaya Meditsina ; 26(4):77-85, 2023.
Article in Russian | EMBASE | ID: covidwho-20242706

ABSTRACT

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.

8.
Revista Medica del Hospital General de Mexico ; 85(2):72-80, 2022.
Article in English | EMBASE | ID: covidwho-20242016

ABSTRACT

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.

9.
Revista Medica del Hospital General de Mexico ; 85(3):120-125, 2022.
Article in English | EMBASE | ID: covidwho-20242015

ABSTRACT

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.

10.
Open Access Macedonian Journal of Medical Sciences ; 11(B):234-238, 2023.
Article in English | EMBASE | ID: covidwho-20241234

ABSTRACT

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.

11.
Infektsionnye Bolezni ; 20(4):12-24, 2022.
Article in Russian | EMBASE | ID: covidwho-20240463

ABSTRACT

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.

12.
Cytotherapy ; 25(6 Supplement):S72, 2023.
Article in English | EMBASE | ID: covidwho-20239522

ABSTRACT

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

13.
Kanzo/Acta Hepatologica Japonica ; 62(7):429-432, 2021.
Article in Japanese | EMBASE | ID: covidwho-20239454

ABSTRACT

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.

14.
Siberian Medical Review ; 2022(3):40-48, 2022.
Article in Russian | EMBASE | ID: covidwho-20239032

ABSTRACT

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.

15.
Journal of SAFOG ; 15(2):199-205, 2023.
Article in English | EMBASE | ID: covidwho-20237185

ABSTRACT

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.

16.
Asian Journal of Pharmaceutical and Clinical Research ; 16(5):13-18, 2023.
Article in English | EMBASE | ID: covidwho-20236199

ABSTRACT

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.

17.
Cancer Research Conference: American Association for Cancer Research Annual Meeting, ACCR ; 83(7 Supplement), 2023.
Article in English | EMBASE | ID: covidwho-20235541

ABSTRACT

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.

18.
Journal of Medicinal and Chemical Sciences ; 6(9):2018-2027, 2023.
Article in English | Scopus | ID: covidwho-20235420

ABSTRACT

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).

19.
Rational Pharmacotherapy in Cardiology ; 19(1):65-70, 2023.
Article in Russian | EMBASE | ID: covidwho-20235021

ABSTRACT

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.

20.
Cancer Research Conference: American Association for Cancer Research Annual Meeting, ACCR ; 83(7 Supplement), 2023.
Article in English | EMBASE | ID: covidwho-20234125

ABSTRACT

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.

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