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Background & Aim: With larger accessibility and increased number of patients being treated with CART cell therapy, real-world toxicity continues to remain a significant challenge to its widespread adoption. We have previously shown that allogeneic umbilical cord blood derived (UCB) regulatory T cells (Tregs) can resolve uncontrolled inflammation and can treat acute and immune mediated lung injury in a xenogenic model as well as in patients suffering from COVID-19 acute respiratory distress syndrome. The unique properties of UCB Tregs including: i) lack of plasticity when exposed to inflammatory micro-environments;ii) no requirement for HLA matching;iii) long shelf life of cryopreserved Tregs;and iv) immediate product availability for on demand treatment, makes them an attractive source for treating acute inflammatory syndromes. Therefore, we hypothesized that add-on therapy with UCB derived Tregs may resolve uncontrolled inflammation responsible for CART cell therapy associated toxicity. Methods, Results & Conclusion(s): UCB Tregs were added in 1:1 ratio to CART cells, where no interference in their ability to kill CD19+ Raji cells, was detected at different ratios : 8:1 (80.4% vs. 81.5%);4:1 (62.0% vs. 66.2%);2:1 (50.1% vs. 54.7%);1:1 (35.4% vs. 44.1%) (Fig 1A). In a xenogenic B cell lymphoma model, multiple injections of Tregs were administered after CART injection (Fig 1B), which did not impact distribution of CD8+ T effector cells (Fig 1C) or CART cells cells (Fig 1D) in different organs. No decline in the CAR T levels was observed in the Tregs recipients (Fig 1E). Specifically, no difference in tumor burden was detected between the two arms (Fig 2A). No tumor was detected in CART+Tregs in liver (Fig 2B) or bone marrow (Fig 2C). A corresponding decrease in multiple inflammatory cytokines in peripheral blood was observed in CART+Tregs when compared to CART alone (Fig 2D). Here we show "proof of concept" for add-on therapy with Tregs to mitigate hyper-inflammatory state induced by CART cells without interference in their on-target anti-tumor activity. The timing of Tregs administration after CART cells have had sufficient time for forming synapse with tumor cells allows for preservation of their anti-tumor cytotoxicity, such that the infused Tregs home to the areas of tissue damage to bind to the resident antigen presenting cells which in turn collaborate with Tregs to resolve inflammation. Such differential distribution of cells allow for a Treg "cooling blanket" and lays ground for clinical study. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy
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Objectives: Data about COVID-19 patients treated with veno-arterial-ECMO (VA-ECMO) is limited. Reported survival rates range from 27.9% to 77.8%, depending on VA-ECMO indication. A subgroup of patients suffers from circulatory failure due to a COVID-19 associated hyperinflammatory state (CovHI). In these patients, differentiation between inflammation and sepsis is difficult but important. In this retrospective case series, differential diagnoses of COVID-19 associated refractory circulatory failure and survival rates in different indications for VA-ECMO are investigated. Method(s): Retrospective analysis of 28 consecutive COVID-19 patients requiring VA-ECMO at the University Hospital Regensburg between March 2020 and May 2022. Specific treatment for COVID-19 was in accordance with respective guidelines. Mycotic infections were either invasive or met current definitions of COVID19-associated-pulmonary aspergillosis. Result(s): At VA-ECMO initiation, median age was 57.3 years (IQR: 51.4 - 61.8), SOFA score 16 (IQR: 13 - 17) and norepinephrine dosing 0.53mug/kg/min (IQR: 0.32 - 0.78). Virus-variants were: 61% wild-type, 14% Alpha, 18% Delta and 7% Omicron. Survival to hospital discharge was 39%. 17 patients were primarily supported with VA-ECMO only (survival 42%), 3 patients were switched from VV to VA-ECMO (survival 0%), and 8 patients were converted from VA to VAV or VV-ECMO (survival 50%). Indications for VA-ECMO support were pulmonary embolism (PE) (n=5, survival 80%), right heart failure due to secondary pulmonary hypertension (n=5, survival 20%), cardiac arrest (n=4, survival 25%), acute left heart failure (ALHF) (n=11, survival 36%) and refractory vasoplegia (n=3, survival 0%). Inflammatory markers at VA-ECMO initiation were higher in patients with ALHF or vasoplegia;in these patients a higher rate of invasive fungal infections (10/14, 71% vs. 4/14, 29%;p=0.023) compared to the other patients was found. Conclusion(s): Survival on VA-ECMO in COVID-19 depends on VA-ECMO indication, which should be considered in further studies and clinical decisions making. Circulatory failure due to vasoplegia should be considered very carefully as indication for VA-ECMO. A high rate of mycotic infections mandates an intense microbiological workup of these patients and must be considered as an important differential diagnosis to CovHI.
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Red bone marrow samples investigation in deceased COVID-19 patients enabled to identify the phenomena of secondary hemophagocytosis. Analysis of the data showed that phagocytic reactions during infection of patients with SARS-CoV-2 are manifested both in relation to erythrocytes and leukocytes. The data obtained make it possible to expand the strategy of therapeutic measures, taking into account the new data on the mechanisms of the pathogenesis of COVID-19 in severe viral infection based on morphological findings and additional information on the involvement of young erythrocytes and lymphocytes in the structure of the red bone marrow in the cascade of pathological reactions. The results obtained confirm a wide range of aggressive damaging effects of SARS-CoV-2 in the development of multiple organ failure against the background of COVID-19 and the involvement of the red bone marrow in the pathological process. The authors supplemented information about the mechanisms of hypoxia in COVID-19, which is not only a consequence of damage to the respiratory epithelium, but also the result of damage to erythrocyte differons both at the level of red bone marrow and in peripheral blood. This fact must be taken into account in the development of a treatment strategy and in the creation of new drugs for the treatment of infected patients with various strains of SARS-CoV-2.
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The Severe Acute Respiratory Syndrome Coronavirus-2 causes a dreadful Coronavirus Disease namely COVID-19. Respiratory system is the primary target of the virus. It also impairs other major organs such as kidney, heart, liver, brain etc. Multiple novel variants of SARS-CoV-2 have appeared since the SARS-CoV-2 pandemic occurred which are linked to increased virulence, disease transmission and severity. The virus attacks the host signalling pathways to maintain a favourable environment for its spread. The present study focuses on the comprehensive analysis of major signaling pathways affected due to several variants of SARS-CoV-2 leading to abnormalities in cell growth and differentiation. The information was curated from the weblinks of several platforms like WHO, CDC, PANGO, Nextstrain clade and GISAID clade. The data on signaling pathways and comorbidities was generated by screening of different research and review articles. SARS-CoV-2 consolidates the cytoskeleton of the host for effective cell invasion and modulates the transcription processes to enable the translation of viral protein(s). These events lead to significant increase and prolonged hyper inflammation. Further, a decreased interferon (IFN) response along with increased interleukin production leading to cytokine storm is observed. Deregulation of interleukin pathways, TNF-alpha signalling through JAK/STAT-3 signalling, MAPK1, mTOR, PI3K are few other signalling pathways that are affected on SARS-CoV-2 infection. This review represents a comprehensive analysis of the vigorous life cycle of SARS CoV-2, its different variants affecting host signalling pathways which eventually cause dysfunctioning of several organs and development of comorbidities.
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Introduction: During the Covid-19 pandemic, 540,895 people were identified as immunosuppressed and believed to be at increased risk of severe disease.1 As the pandemic evolved, biologic immunosuppression became a treatment of severe Covid-19.2 The true impact of immunosuppression on disease severity remains unclear. Objective(s): 1. Identify the incidence of immunosuppressed patients admitted to the ICU. 2. Analyse the mortality of those who are immunocompetent and immunosuppressed. 3. Examine the differences in mortality and level of care required between sub groups of patients on immunosuppression;those on biologics, non-biologics, and a combination of both. Method(s): A retrospective search of all Covid-19 positive admissions from March 2020 to November 2021 across two adult ICUs at Chelsea & Westminster NHS Trust was performed, using the EPR system. We identified those on immunosuppressive drugs, the level of care they required, and 28 day mortality. We categorised different types of immunosuppression, vaccination status, if applicable and co-morbidities. The exclusion criteria were primarily those with false positive swabs or incomplete data. Result(s): Baseline characteristics were median age (56 vs 56), and APCHE II score (20.08 in the immunosuppressed group vs 14.0 in immunocompetent). Thirteen immunosuppressed patients were identified. Reasons for drug immunosuppression in this group included solid organ transplant (6/13), and autoimmune conditions (7/13). Two patients were on biologic drugs alone, 8 were on non-biologics, and 3 were on a combination. Four of this group had received at least 2 doses of a Covid-19 vaccine. Mortality was 61.54% (8/13) in the immunosuppressed group vs 36.65% (199/543) in the immunocompetent group. Conclusion(s): Despite similar demographics, patients on immunosuppression had a significantly higher mortality than the immunocompetent group. Interestingly, those on targeted biological immunosuppression had the lowest incidence of requiring level 3 care, and no deaths. It is a possibility that biologics dampen the hyper-inflammation seen in severe Covid-19 pneumonitis, raising the question of a possible protective benefit from severe disease. This reflects the findings of the REMAP-CAP investigators,3 who showed that the IL-6 inhibiting biologics Tocilizumab and Sarilumab are efficacious against the most severe disease following admission to ICU with Covid-19 pneumonitis. The single centre and retrospective observational design, combined with small numbers on immunosuppression, despite a large inclusion criterion, mean it is not possible to make statistical conclusions. Confounding factors include the effects of vaccination, shielding and the change in SARS-CoV-2 variant prevalent during different times during the pandemic.
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Lung cancer is the most common cancer in males and the second most common among females both in Europe and worldwide. Moreover, lung cancer is the leading cause of death due to cancer in males. The European region accounts for 23% of total cancer cases and 20% of cancer-related deaths. Relationships have been described between a number of infectious agents and cancers, but our knowledge of the role of viruses, both respiratory and systemic, in the pathogenesis of lung cancer is still rudimentary and has been poorly disseminated. In this chapter, we review the available evidence on the involvement of HPV, Epstein-Barr virus, HIV, cytomegalovirus and measles virus in the epidemiology and pathogenesis of lung cancer.Copyright © ERS 2021.
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It is known that inflammatory cytokines exacerbate the persistence and severity of various disease states. Breast cancer is the most frequently detected cancer among women worldwide and our recent studies suggest that the inflammatory state of breast (BrCa) cancer, a byproduct of elevated cytokine expression, induces epigenetic modifications leading to increased recurrence. Ongoing NCI clinical trial data (ClinicalTrials.gov, CCC19, NCT04354701) indicates that among patients with cancer and COVID-19, the mortality is high, and the most prevalent malignancies are of breast [21%] and prostate [16%] origin. Due to the risk of cytokine storm during SARS-CoV-2 infection, it is crucial to identify potential mechanisms of hyperinflammation in BrCa patients. In this study, we have evaluated the level of copy number alteration (CNA) of different inflammatory cytokines including IL-8, IL-1b, IL6, IL-8, GM-CSF, TNF-alpha and many others using cBioportal platform which includes over sixty-nine thousand tumor samples (n>69,000 from 213 different studies) from over 33 different cancers. We found that IL-8 has the highest level of amplification in different breast cancers subtypes. Besides, we also analyzed serum samples from BrCa patients, both recurrent and non-recurrent, by different proteomics methods to identify serum cytokines involved in prognosis and recurrence. Comparative data analysis between non-recurrent BrCa against recurrent BrCa patients identified several proteins with very high significance, mostly proteins associated with epigenetic pathways including HDAC9 (P = 0.0035), HDAC5 (P = 0.013), and HDAC7 (P = 0.020). Besides, we identified differential expression of several pro-inflammatory cytokines and immune regulators (IL-8, IL-4, IL-18, IL-12p70) that were present only in recurrent BrCa patient serum. Our data indicate that inflammatory processes contribute to epigenetic modifications that ultimately play a critical role in breast cancer recurrence. In terms of COVID-19 associated co-morbidity, the already dysregulated inflammatory state of BrCa patients may increase their susceptibility to cytokine-storm, leading to increased severity of COVID-related complications and increased mortality rate. Specifically, we hypothesize that the identified elevated level of IL-8 in BrCa patients may lead to a higher basal level of inflammation and contribute to the risk of attaining cytokine-storm during SARS-CoV-2 infection, making it a valuable target for future studies.
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Aim: Coronavirus disease 2019 (COVID-19) has become a public health threat to people all over the world in 2020 and 2021. The Centers for Disease Control and Prevention (CDC) and WHO (World Health Organization) have named a novel disease multisystem inflammatory syndrome in children (MIS-C). Herein we aimed to present a group of pediatric patients with MIS-C, who were followed up in our clinic. Material(s) and Method(s): We retrospectively reviewed the medical records of patients who were followed up at our University Hospital with the diagnosis of MIS-C between January 2021 and May 2021. Result(s): The mean age of 9 patients was 87.4 +/-17.8 years (range 6-161 months);six of the patients were male. All patients had fever at admission. The duration of the fever was between 3 and 7 days. Four patients (44.4%) had terminal ileitis on ultrasonic examination. The laboratory tests of the patients revealed leukocytosis in 4 (44.4%) patients, anemia in 5 (55.5%) patients, thrombocytopenia in 1 (11.1%) patient, and a high CRP level in 8 (88.8%) patients. All patients had high sedimentation rates and procalcitonin levels. One (11.1%) patient was operated on for terminal ileitis. All patients were treated with steroids (1-2 mg/kg prednisolone) and IVIG (2gr/kg). Patients who needed ICU admission were also treated with vasoactive drug infusion (intravenous dopamine). Discussion(s): There is a need for increased awareness among pediatricians that MIS-C should come to mind, especially in patients with long-lasting fever and signs and symptoms that resemble Kawasaki disease.Copyright © 2022, Derman Medical Publishing. All rights reserved.
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Vertical transmission of SARS-CoV-2 from mother to fetus is widely accepted. Whereas most infected neonates present with mild symptoms or are asymptomatic, respiratory distress syndrome (RDS) and abnormal lung images are significantly more frequent in COVID-19 positive neonates than in non-infected newborns. Fatality is rare and discordant meta-analyses of case reports and series relating perinatal maternal COVID-19 status to neonatal disease severity complicate their extrapolation as prognostic indicators. A larger database of detailed case reports from more extreme cases will be required to establish therapeutic guidelines and allow informed decision making. Here we report an unusual case of a 28 weeks' gestation infant with perinatally acquired SARS-CoV-2, who developed severe protracted respiratory failure. Despite intensive care from birth with first line anti-viral and anti-inflammatory therapy, respiratory failure persisted, and death ensued at 5 months. Lung histopathology showed severe diffuse bronchopneumonia, and heart and lung immunohistochemistry confirmed macrophage infiltration, platelet activation and neutrophil extracellular trap formation consistent with late multisystem inflammation. To our knowledge, this is the first report of SARS CoV-2 pulmonary hyperinflammation in a preterm newborn with fatal outcome.
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The COVID-19 pandemic has plagued the world for over three years since discovering the causative virus, SARS-CoV-2, in China. The rampant spread of the virus led to the loss of livelihoods of millions across the globe. This public health emergency prompted the rapid development of vaccines and treatments to fight against viral infection. Vaccines against the viral infection started rolling out in late 2020, and the distribution of the vaccines worldwide managed to reduce the symptoms of COVID-19 and prevent outbreaks in local communities. However, COVID-19 infections are still prevalent, with patients suffering from severe symptoms which require oxygen support or mechanical ventilation. Thus, therapeutic agents for COVID-19 play a significant role in reducing the risk of disease progression into severe disease and improving hospitalized patients' clinical outcomes. Existing drugs such as remdesivir, molnupiravir, baricitinib, anakinra, and tocilizumab have been repurposed to treat COVID-19 earlier during the pandemic to meet the urgent demand for treatment. There are also novel antiviral and immunomodulating treatments (nirmatrelvir plus ritonavir, ensitrelvir, regdanvimab, sotrovimab, and vilobelimab) that were developed during the pandemic to fight against COVID-19 infections. These therapeutic agents have been reported to be effective and safe for use to treat COVID-19 infections of different severity. Nevertheless, continuous surveillance is imperative in ensuring that these treatment methods maintain efficacy and safety profiles in treating COVID-19 caused by different variants of the virus. © 2023, HH Publisher. All rights reserved.
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Patients with ANCA-associated vasculitis (AAV) cause extreme alertness during the coronavirus disease 2019 (COVID-19) pandemic, associated with many factors: the initial damage to the respiratory system (upper respiratory tract, lungs) and kidneys, immunosuppressive treatments, difficult prognosis of COVID-19 with the risk of AAV exacerbation. We present a clinical case of a moderate COVID-19 in a patient with granulomatosis with polyangiitis, who received anti-B cell therapy with rituximab (RTX) for a long time. Coronavirus pneumonia developed one year after RTX, while B-lymphocyte depletion persisted. In order to achieve an adequate antiviral immune response and prevent hyperinflammation, treatment was carried out with antiviral drugs, anticoagulants, convalescent plasma, human normal immunoglobulin, and interleukin-6 antagonist tocilizumab. Possible predictors of severe COVID-19 in patients with AAV are discussed.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
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Background/Aims Haemophagocytic lymphiohistiocytosis (HLH) is a rare, underrecognised hyperinflammatory syndrome, characterised by immune dysregulation. Without treatment, the ensuing cytokine storm leads to high mortality. Secondary HLH (sHLH) is triggered by malignancy, infection, autoimmunity and medicines;treatment with immunosuppression is consensus- rather than evidence-based and extrapolated from primary HLH. Sheffield hosts a mature HLH multidisciplinary advisory group (MDAG). Here we evaluate the cause, treatment, requirement for critical care and mortality of people with HLH managed through the MDAG in a period including the coronavirus pandemic but prior to NHS England approval of anakinra (IL-1 antagonist) for HLH. Methods This retrospective evaluation (approved locally STH 10850) identified patients from MDAG records 1st October 2016 to 30th September 2021. Data from electronic/paper records was analysed using Microsoft Excel. Results HLH triggers were infection (viral 34%, bacterial 10%), haematological (35%), rheumatological (13%) and other (8%). Rheumatological causes were Still's disease (n=5);antiphospholipid syndrome (n=2);JO1 dermatomyositis (n=1);SLE (n=1);and rheumatoid arthritis (n=1). Other causes included unknown (n=3);combined systemic JIA and sickle cell crisis (n=1);medication (alemtuzumab) (n=1);and primary HLH (n=1). Overall mortality was 53% and highest in HLH with a haematological malignancy trigger (82%) Prior to the COVID19 pandemic (pre-March 2020), the commonest trigger of HLH was haematological malignancy (47%);after March 2020, the commonest trigger was infection (64%);COVID-19 explained 42% of cases. Mortality fell from 72% to 31%. Conclusion In this real-world series of people with HLH, mortality and critical care requirement was high. HLH triggers reflect published evidence as does poor prognosis in haematological malignancy-associated HLH. No-HLH associated with non-haematological malignancy was identified;we may need to improve MDAG reach into oncology. Seeming reduction in mortality following the COVID-19 pandemic may reflect increased recognition of COVID-19 induced hyperinflammation along with locallyagreed access to anakinra for COVID-19-induced HLH. The increase in infection related HLH cases since March 2020 is explained largely by COVID-19 cases. This has led to a relative reduction in cases related to haematological malignancy. HLH requires multidisciplinary management and better research to improve treatment. (Table Presented).
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The Novel Coronavirus Disease (COVID-19) is characterized by a variety of clinical manifestations, including a predominant lesion of the respiratory system with the possible development of distress syndrome, the development of multiple organ failure. COVID-19 can cause depression, anxiety, and other emotional disorders, which may interfere with subsequent physical recovery. The aim - clinical analysis of emotional disorders in patients with the Novel Coronavirus Infection (COVID-19). Material and methods. A retrospective analysis of electronic medical records of 124 patients admitted to the infectious diseases department of Chelyabinsk City Clinical Hospital No. 8 in 2020-2021 was carried out. The methods of clinical and psychological research (including clinical conversation, observation and testing using the "Hospital Scale of Anxiety and Depression" HADS and the "Symptom Check List" SCL-90-R) were used to identify the features of the emotional states of patients with COVID-19. Statistical analysis was performed using the statistical package <<Statistica 6.0>>. The Spearman rank correlation coefficient was used. Results. Typical complaints upon admission to the hospital are fever, cough, general weakness, loss of smell and taste, runny nose. The majority of patients showed elevated levels of C-reactive protein and protein of the acute phase of inflammation - ferritin, an increase in the D-dimer by more than 2.5 times compared with the average standard values, a decrease in the value of the prothrombin index (mean value 88.7+/-6.4%) indicate coagulopathy as a manifestation of hyperinflammation that develops in COVID-19. More than half of patients (52.08+/-9.42%) experienced psychological distress of moderate and high severity: an increased level of distress was recorded in 42.78+/-9.33% of the examined patients, a high level of distress was found in 9.30+/-5.48% of patients. Direct correlations of varying degrees of strength between general somatic distress and indicators of anxiety, depression, psychopathological manifestations (obsessive-compulsiveness and interpersonal sensitivity) and mental distress were identified. Revealed negative emotional experiences in patients with COVID-19 can cause adverse effects on the course and prognosis of the disease, reduce adherence to treatment, negatively affect the social functioning and quality of life of patients.Copyright © Infectious Diseases: News, Opinions, Training 2022.
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Context: The coronavirus disease 2019 (COVID-19) pandemic is still a cause of worldwide health concern. Diabetes and its associated comorbidities are risk factors for mortality and morbidity in COVID-19. Selecting the right antidiabetic drug to achieve optimal glycemic control might mitigate some of the negative impacts of diabetes. Metformin continues to be the most widely administered antidiabetic agent. There is evidence of its beneficial outcome in COVID-19 independent of its glucose-lowering effect. Evidence Acquisition: A thorough literature search was conducted in PubMed, Google Scholar, Scopus, and Web of Science to identify studies investigating metformin in COVID-19. Result(s): Several overlapping mechanisms have been proposed to explain its antiviral properties. It could bring about conformational changes in the angiotensin-converting enzyme-2 receptor and decrease viral entry. The effects on the mammalian target of the rapamycin pathway and cellular pH have been proposed to reduce viral protein synthesis and replication. The immunomodulatory effects of metformin might counter the detrimental effects of hyperinflammation associated with COVID-19. Conclusion(s): These findings call for broader metformin usage to manage hyperglycemia in COVID-19.Copyright © 2023, International Journal of Endocrinology and Metabolism.
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Acute respiratory viral infections (ARVI) are the most common illnesses worldwide. In some instances, mild cases of ARVI progress to hyperinflammatory responses, which are damaging to pulmonary tissue and requiring intensive care. Here we summarize available information on preclinical and clinical effects of XC221GI (1-[2-(1-methyl imidazole-4-yl)-ethyl]perhydroazin-2,6-dione), an oral drug with a favorable safety profile that has been tested in animal models of influenza, respiratory syncytial virus, highly pathogenic coronavirus strains and other acute viral upper respiratory infections. XC221GI is capable of controlling IFN-gamma-driven inflammation as it is evident from the suppression of the production of soluble cytokines and chemokines, including IL-6, IL-8, CXCL10, CXCL9 and CXCL11 as well as a decrease in migration of neutrophils into the pulmonary tissue. An excellent safety profile of XC221GI, which is not metabolized by the liver, and its significant anti-inflammatory effects indicate utility of this compound in abating conversion of ambulatory cases of respiratory infections into the cases with aggravated presentation that require hospitalization. This drug is especially useful when rapid molecular assays determining viral species are impractical, or when direct antiviral drugs are not available. Moreover, XC221GI may be combined with direct antiviral drugs to enhance their therapeutic effects.
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A patient presented with COVID-19-induced enteritis and colitis associated with a high D-dimer. Serotonin released by activated platelets can lead to inflammation and multiorgan failure in COVID-19 infection. Cyproheptadine blocks serotonin receptors. In light of a prior report that showed that cyproheptadine successfully treated neurologic sequelae in COVID-19, we applied this treatment to this patient. Rapid clinical improvement and reduction of D-dimer occurred after 3 doses of cyproheptadine. This inexpensive, well-Tolerated, oral medication may be applicable to treat hyperinflammatory sequelae of COVID-19 infection.Copyright © 2023 American College of Gastroent. All rights reserved.
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Patients with ANCA-associated vasculitis (AAV) cause extreme alertness during the coronavirus disease 2019 (COVID-19) pandemic, associated with many factors: the initial damage to the respiratory system (upper respiratory tract, lungs) and kidneys, immunosuppressive treatments, difficult prognosis of COVID-19 with the risk of AAV exacerbation. We present a clinical case of a moderate COVID-19 in a patient with granulomatosis with polyangiitis, who received anti-B cell therapy with rituximab (RTX) for a long time. Coronavirus pneumonia developed one year after RTX, while B-lymphocyte depletion persisted. In order to achieve an adequate antiviral immune response and prevent hyperinflammation, treatment was carried out with antiviral drugs, anticoagulants, convalescent plasma, human normal immunoglobulin, and interleukin-6 antagonist tocilizumab. Possible predictors of severe COVID-19 in patients with AAV are discussed.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
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The immunological reaction that facilitates the cytokine storm in the infection by the new coronavirus facilitates the appearance of microvascular, endothelial and direct cellular damage, which leads to a prothrombotic state and events of thromboembolism to different apparatus and systems as a complication. Therefore, the need to provide adequate prophylactic therapy or anticoagulant management in time and adequate dosage to these patients, as well as an individualized coagulation and hemostasis study. This document is intended to summarize in a practical way the evidence published to date and provide a broader view of the pathophysiological phenomena that occur in this hyperinflammatory state that has taught us a lot since its arrival.Copyright © 2022 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.
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Introduction: The aim of our study is to evaluate the relationship between dexmedetomidine (DEX) use as a sedative agent in mechanical ventilated ICU patients and 28-day mortality. DEX, a selective alfa-2 adrenergic receptor agonist, widely used for its sedative and analgesic properties, has been linked to increasing parasympathetic tone, reducing the inflammatory response and oxidative stress [1]. Since severe COVID-19 is associated with an hyperinflammatory state, it is hypothesized that DEX might improve outcomes in these patients. Method(s): This is a retrospective observational study of mechanically ventilated patients admitted with COVID-19 pneumonia in the ICU of a tertiary center in Portugal, between March 2020 and December 2021. Logistic regression analysis was performed to evaluate the association of DEX use and 28-day mortality from time of intubation. Result(s): A total of 277 patients were analyzed, 151 in the DEX group and 126 in the no DEX group. Patients in the DEX group were younger (53.3 vs. 63.3 years, p < 0.001), had less comorbidities (2.8 vs. 3.5, p = 0.01), lower SOFA at admission (6.2 vs. 7.1, p = 0.01) but had a prolonged ICU stay (21.4 vs. 15.9, p < 0.001). Male gender (65.6 vs. 69.0, p = 0.54), incidence of obesity (56.3 vs. 46.8, p = 0.12), coronary artery disease (4.0 vs. 7.9, p = 0.16) and atrial fibrillation (4.0 vs. 7.1, p = 0.25) were similar between groups. PaO2/ FiO2 ratio at admission (111.1 vs. 108.1, p = 0.61), days spent in RASS < 3 (13.7 vs. 12.4, p = 0.31) and opioid use (14.8 vs. 13.1, p = 0.16) were also similar. From time of intubation, 28-day mortality in the cohort receiving DEX was 14.7% compared to 59.5% in the no DEX group (OR 0.12;95% CI 0.07-0.21;p = 0.01). Conclusion(s): Use of DEX was associated with lower 28-day mortality in COVID-19 critically ill patients requiring invasive mechanical ventilation in our study analysis. Considering the limitations of a retrospective observational study, RCTs are needed to confirm the results.