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2.
Glycobiology Conference ; 32(11), 2022.
Article in English | EMBASE | ID: covidwho-2124568

ABSTRACT

The proceedings contain 195 papers. The topics discussed include: structural and mechanistic studies of C-mannosyltransferase;development of radical carbohydrate footprinting for glycan solvent accessible surface analysis;GlycoGrip: a glycocalyx-inspired lateral flow strip-based assay designed to detect betacoronaviruses;glycans as central regulators of the immunological pathways at the frontiers of microbial infections, chronic inflammation and autoimmunity;an atlas of the human O-Man glycoproteome reveals domain-specific modifications and substrate specificities of human mannosyltransferases;role of proteoglycans in determining muscle stem cell fate during pregnancy;transcriptomic analyses unravel differential expression of genes involved in the N-glycosylation pathway of phaeodactylum tricornutum ecotypes;immunoglobulin N-glycosylation discriminates acute Lyme disease from endemic healthy controls and mimic diseases ' a novel diagnostic and prognostic;spatiotemporal biosynthesis of paucimannosidic proteins via a noncanonical truncation pathway in human neutrophils;and specific N-glycans regulate the function of an extracellular adhesion complex during somatosensory dendrite patterning.

3.
British Journal of Surgery ; 109(Supplement 5):v47, 2022.
Article in English | EMBASE | ID: covidwho-2134938

ABSTRACT

Aims: Cholecystectomy is one of The most frequently performed operations in The United Kingdom. Following The spread of COVID19 infection, reduced operational capacity has led to lengthen The waiting time for cholecystectomy, which leads to significant readmission rate, growing financial burden and increased complexity of The surgical intervention. Our study aims to identify changes in gallbladder (GB) histopathological findings before and during COVID19 pandemic. Method(s): Data was collected retrospectively on 337 patients who underwent cholecystectomy between 01/2019-12/2019 (pre-COVID19) and 296 patients between 09/2020-10/2021 (during COVID19) at Princess Alexandra Hospital, including preoperative clinical-radiological, Surgery waiting time, operation details, postoperative histology and complications. Statistical analysis performed using chi-square tests (p-value<0.001). Result(s): A total of 2 (0.6%) female cases (average age 75.6) had gallbladder dysplasia (GD) and 1 of them had GB adenocarcinoma found pre-COVID19 versus 8 (2.7%) (7F:1M, average age 46.6) with GD and 5 (1.7%) (3F:2M, average age 72.6) with adenocarcinoma during pandemic. Other histopathological findings were 153 (45.4%) GB with chronic inflammation, 2 (0.5%) with necrosis or perforation pre-COVID19 versus 127 (42.9%) and 6 (2%) respectively during pandemic. The average Surgery waiting time for patients with GD or adenocarcinoma was 135 days before COVID19 versus 224.21 (33-676) during pandemic. Conclusion(s): GD is associated with increased Cancer risk at GB and other biliary tract sites. Our data demonstrated a statistically significant increase of incidence of GD and adenocarcinoma (p-value<0.00089) in patients who underwent cholecystectomy during pandemic versus pre-COVID19. Further ongoing study is recommended to understand The correlation with prolonged Surgery waiting time.

4.
Investigacion Clinica (Venezuela) ; 63(4):435-453, 2022.
Article in English | EMBASE | ID: covidwho-2114901

ABSTRACT

Angiotensin II (Ang II) is a hormone and the main effector of the renin-angiotensin system (RAS). This peptide has crucial pathophysiologi-cal effects on hypertension, cardiac hypertrophy, endothelial proliferation, inflammation and tissue remodelling through G protein-coupled receptors. The pro-inflammatory role of Ang II has been reported in various inflammatory pro-cesses. Obesity is linked to a chronic inflammatory process which in turn is the cause of some of its morbidities. Ang II is related to the comorbidities related to the comorbidities of obesity, which include alterations in the heart, kid-ney, hypertension and coagulation. In this regard, activation of AT1 receptors by Ang II can induce an inflammatory process mediated by the transcription factor NF-kB, triggering inflammation in various systems that are related to the comorbidities observed in obesity. The aim of this review was to highlight the pro-inflammatory effects of Ang II and the alterations induced by this hormone in various organs and systems in obesity. The search was done since 1990 through Medline, EMBASE and PubMed, using the keywords: angiotensin II;an-giotensin II, obesity;angiotensin II, kidney, obesity;angiotensin II, coagulation, obesity;angiotensin II, inflammation, obesity;angiotensin II, adipose tissue, obesity;angiotensin II, hypertension, obesity;angiotensin II, insulin resistance, obesity;angiotensin II, adiponectin, leptin, obesity;angiotensin II, COVID-19, obesity. Angiotensin II through its interaction with its AT1 receptor, can induce alterations in diverse systems that are related to the comorbidities observed in obesity. Therapeutic strategies to decrease the production and action of Ang II could improve the clinical conditions in individuals with obesity. Copyright © 2022, Instituto de Investigaciones Clinicas. All rights reserved.

5.
Pathogens ; 11(10)2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2071677

ABSTRACT

Due to the presence of the ACE2 receptor in different tissues (nasopharynx, lung, nervous tissue, intestine, liver), the COVID-19 disease involves several organs in our bodies. SARS-CoV-2 is able to infect different cell types, spreading to different districts. In the host, an uncontrolled and altered immunological response is triggered, leading to cytokine storm, lymphopenia, and cellular exhaustion. Hence, respiratory distress syndrome (ARDS) and systemic multi-organ dysfunction syndrome (MODS) are established. This scenario is also reflected in the composition of the microbiota, the balance of which is regulated by the interaction with the immune system. A change in microbial diversity has been demonstrated in COVID-19 patients compared with healthy donors, with an increase in potentially pathogenic microbial genera. In addition to other symptoms, particularly neurological, the occurrence of dysbiosis persists after the SARS-CoV-2 infection, characterizing the post-acute COVID syndrome. This review will describe and contextualize the role of the immune system in unbalance and dysbiosis during SARS-CoV-2 infection, from the acute phase to the post-COVID-19 phase. Considering the tight relationship between the immune system and the gut-brain axis, the analysis of new, multidistrict parameters should be aimed at understanding and addressing chronic multisystem dysfunction related to COVID-19.

6.
Indian Journal of Forensic Medicine and Toxicology ; 16(3):63-68, 2022.
Article in English | EMBASE | ID: covidwho-2067687

ABSTRACT

Background: COVID-19 is a pandemic disease caused by droplet infection from SARS-CoV-2. Due to its rapid transmission and high case fatality rate, the identification of risk factors and prognostic factors is important. Obesity is a risk factor for poor outcomes in COVID-19. It is associated with chronic inflammation, disorders of the immune system. Obesity can be determined based on BMI. Chest X-Ray is supported in establishing the diagnosis and prognosis of COVID-19 patients. Assessment of the severity index of Chest X-Ray radiographs can use the Modified Chest X-Ray Scoring System of RSUP Dr. Soetomo. This study was conducted to analyze the relationship between BMI and chest radiography severity index in hospitalized COVID-19 patients at dr. Mohammad Hoesin Palembang in 2021. Methods: This research used a cross-sectional analytic observational design. Sampling was done using a consecutive sampling technique with 70 samples and obtained from the patient's medical record. The data were analyzed by univariate and bivariate (Chi-Square) using IBM SPSS Statistics 26 software. Results: Patients with BMI Overweight-Obesity had more in Moderate-Severe (18.6%) radiographic severity index scores (18.6%) than Normal-Mild (15.7%). Chi-Square bivariate analysis, BMI (p=0.033;p-value <0.05) had a significant relationship with the chest radiographic severity index with Odds Ratio 3,00, 95% CI (1,073–8,386). Conclusion: There is a significant relationship between body mass index and chest radiography severity index in COVID-19 patients. Overweight-Obesity BMI patients have a 3-fold chance of having a Moderate-Severe category of radiographic severity index compared to Underweight-Normal BMI patients.

7.
Wound Repair and Regeneration ; 30(5):A3, 2022.
Article in English | EMBASE | ID: covidwho-2063960

ABSTRACT

Background: It has long been known that the fetal response to skin injury is regenerative, with a lack of abnormal collagen deposition or scar, and restoration of normal dermal architecture. This response is associated with minimal inflammation.We have shown that the decreased inflammation is due to decreased production of pro-inflammatory cytokine production compared to the adult response. In addition, we have shown fetal tendon and the fetal heart can heal by regeneration, with restoration of structure and function, and is also associated with decreased proinflammatory cytokine production and decreased inflammation. We hypothesized that strategies targeting inflammation and associated oxidative stress could be used in adult diseases. We have identified diabetic wounds, acute lung injury, and colitis where inflammation and oxidative stress plays a central role in the pathogenesis the disease. Material(s) and Method(s): We have developed a novel strategy using nanotechnology to target inflammation and oxidative stress. We have conjugated novel cerium oxide nanoparticles, which act as potent scavengers of reactive oxygen species, to the anti-inflammatory microRNA miR146a, which suppresses the NFkB pathway and the production of the pro-inflammatory cytokines IL-6 and IL-8. Result(s): In diabetic wounds, impaired healing is associated with chronic inflammation and oxidative stress. We have demonstrated, in both small and large diabetic animals models, that CNP-miR146a can decrease inflammation and oxidative stress and correct the diabetic wound healing impairment and promote regeneration, similar to rates of healing in non-diabetic animals. We have also examined other disease states where inflammation and oxidative stress is pathogenic. Following acute lung injury, inflammation and oxidative stress leads to the development of adult respiratory distress syndrome or ARDS, the number one cause of mortality with COVID-19, and is associated with a 30-50% mortality. Inflammation and oxidative stress play a central role in the pathogenesis of ARDS. We have shown in models of acute lung injury, including bleomycin, LPS, MRSA, ventilator induced lung injury (VILI) and mustard gas, that CNP-miR146a decreases inflammation and oxidative stress, promotes regeneration and restoration of function, and decreased mortality. Finally, pathogenic inflammation plays a central role in the development of colitis or inflammatory bowel disease. We have shown that CNP-miR146a enemas can prevent progression of disease, restore weight gain, and lacks the adverse effects of systemic immunosuppression. Conclusion(s): We have used our understanding of the mechanisms of fetal regeneration following injury, which progresses with minimal inflammation and oxidative stress, to develop strategies targeting these processes to promote regeneration in adult disease.

8.
The Lancet Gastroenterology and Hepatology ; 7(10):912, 2022.
Article in English | EMBASE | ID: covidwho-2062056
9.
Chest ; 162(4):A575, 2022.
Article in English | EMBASE | ID: covidwho-2060636

ABSTRACT

SESSION TITLE: Uncommon Presentations and Complications of Chest Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Cryptococcus is a ubiquitous fungus in the environment. Infections can occur in humans when Cryptococcus is aerosolized and inhaled. Severity of clinical presentation varies from asymptomatic pulmonary colonization to disseminated life-threatening infection such as meningitis. These infections usually occur with deficiencies in T-cell-mediated immunity, including those with HIV/AIDS and immunosuppression due to transplantation. Herein we present a case of isolated pulmonary cryptococcosis in an immunocompetent host. CASE PRESENTATION: The patient is a 36-year-old never-smoker male with history of recurrent left spontaneous pneumothorax status post VATS blebectomy, negative for alpha-1 antitrypsin deficiency and cystic fibrosis. A year later, he presented with fatigue, shortness of breath, and dry cough after a recent trip to Ohio. Viral panel including COVID-19 was negative. A chest x-ray showed a new 4 cm rounded opacity in the right middle lobe (RML). A CT scan of the chest showed 2 mass-like and nodular areas of consolidation with surrounding GGOs within the RML (Figure 1). He underwent navigational bronchoscopy with transbronchial biopsy (TBBx) of RML, BAL, and EBUS with transbronchial needle aspiration (TBNA). Cytology was negative for malignant cells. BAL showed rare yeast. Pathology of the TBBx showed the airway wall with chronic inflammation including granulomatous inflammation, positive for yeast, most consistent with Cryptococcus with positive Grocott methenamine silver (GMS) stain (Figure 2). Culture of the TBNA grew C. neoformans var. grubii. Other cultures were negative. Serum Cryptococcal antigen was positive. HIV test was negative. He started treatment with oral fluconazole with improvement of symptoms. DISCUSSION: Clinical presentation of pulmonary cryptococcosis can include a variety of symptoms in which immune status is critical for determining the course of infection. Infection can vary from asymptomatic infection to severe pneumonia and respiratory failure, and meningitis. Similarly, imaging findings can also vary and be characterized as pulmonary nodules, consolidations, cavitary lesions, and/or a diffuse interstitial pattern. The diagnosis of Cryptococcus is made using histology, fungal cultures, serum cryptococcal antigen, and radiography in the appropriate clinical and radiological context. Treatment recommendations are determinant on immune status of the patient as well as symptoms. Asymptomatic and localized disease in immunocompetent patients can be monitored and mild/moderate disease can be treated with fluconazole. Those with severe or disseminated infection warrant induction therapy with an amphotericin B and flucytosine CONCLUSIONS: Clinical and radiological presentation of cyptococcosis varies depending on immune status. Disease can occur in both immunocompromised and competent hosts. Immune status determines disease course and treatment. Reference #1: Huffnagle GB, Traynor TR, McDonald RA, Olszewski MA, Lindell DM, Herring AC, et al. Leukocyte recruitment during pulmonary Cryptococcus neoformans infection. Immunopharmacology. 2000 Jul 25;48(3):231–6. Reference #2: Kd B, Jw B, Pg P. Pulmonary cryptococcosis. Semin Respir Crit Care Med [Internet]. 2011 Dec [cited 2022 Apr 2];32(6). Available from: https://pubmed.ncbi.nlm.nih.gov/22167400/ Reference #3: Ms S, Rj G, Ra L, Pg P, Jr P, Wg P, et al. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am [Internet]. 2000 Apr [cited 2022 Apr 1];30(4). Available from: https://pubmed.ncbi.nlm.nih.gov/10770733/ DISCLOSURES: No relevant relationships by Mina Elmiry No relevant relationships by Brenda Garcia No relevant relationships by Zein Kattih no disclosure on file for Priyanka Makkar;No relevant relationships by Jonathan Moore

10.
European Journal of Molecular and Clinical Medicine ; 9(4):2279-2285, 2022.
Article in English | EMBASE | ID: covidwho-2057977

ABSTRACT

Background: The COVID- 19 infections are associated with wide range of bacterial and fungal co-infections. They may be associated with various comorbidities. Definite diagnosis requires demonstration of fungi in tissue sections or in culture. Yield of organism in culture is suboptimal. Hence histopathology plays critical role in establishing the diagnosis and provide evidence of tissue invasion. Objective(s): To study the histopathological features of fungal infections in sino nasal, oral and orbital area associated with COVID-19 patients. Material(s) and Method(s): One hundred twenty cases of fungal infections involving sinonasal, oral and orbital area in laboratory confirmed COVID-19 positive patients between June-September 2021 were taken for study. Clinical data was recorded, histopathological examination was done along with periodic acid Schiff stain and culture report was obtained. Result(s): The study included 92(76.6%) males and 28(23.3%) females with age ranging from 13 to 78 years. The tissues included debridement, biopsy and excision specimen. Acute inflammation was seen in 8(6.66%) cases, chronic inflammation in 112(93.33%), granulomas in 25, thrombosis in 14, necrosis in 104, angioinvasion in 13, perineuritis in 10 and bone invasion in 18 cases. Mixed fungal infection was seen in 11cases. Conclusion(s): Histopathology remains the mainstay in diagnosis of invasive fungal infections especially when culture is negative. Copyright © 2022 Ubiquity Press. All rights reserved.

11.
Journal of Comprehensive Pediatrics ; 13(Supplement 1):17, 2022.
Article in English | EMBASE | ID: covidwho-2057973

ABSTRACT

Multisystem inflammatory syndrome in children (MISC) is a hyperinflammatory state that occurs about two to four weeks after the SARS CoV-2 in the human body. It can potentially involve any organ and cause Kawasaki-like disease, shock with or without ventricular dysfunction, and fever with inflammation. The treatment includes some medications depending on the patient's situation. Asymptomatic children and mild COVID-19 do not need the anti-rheumatic agents. In some moderate and severe COVID-19, the management includes intravenous immune globulin (IVIG) and corticosteroids. The first trial of corticosteroid begins with low to moderate doses, and in refractory cases, it switches to high doses of intravenous methylprednisolone for 1 - 3 consecutive days. In contrast to classic Kawasaki disease, the second dose of IVIG is not recommended in IVIG-resistant cases because of volume overload. In refractory disease or in patients who cannot receive glucocorticoids, there may be rationality for the usage of biologic agents after consulting with a pediatric rheumatologist. The refractory disease could include any of the following: persistent fever more than 24 hours post-treatment., ferritin more than 1000 ng/mL posttreatment, worsening echocardiographic findings, and physician global discretion if the patient fails to improve. High dose Anakinra should be considered the first choice for treatment of MIS-C refractory to IVIG and glucocorticoids in patients with MIS-C and features of macrophage activation syndrome (MAS) or patients with contraindications to long-term use of corticosteroids. Infliximab may be used as an alternative biologic agent in these situations except in features of MIS-C and MAS. Furthermore, infliximab may be considered second-line therapy in patients with MIS-C who have persistent inflammation or myocardial dysfunction. Some researchers recommend it in conjunction with IVIG as initial therapy, although further data are needed.

12.
Current Topics in Nutraceutical Research ; 20(4):662-665, 2022.
Article in English | EMBASE | ID: covidwho-2044385

ABSTRACT

Interactions of platelets with circulating cells and vessel walls are implicated in various inflammatory processes. In certain circumstances, the hemostatic and inflammatory functions of platelets may overlap. Platelet-lymphocyte/leukocyte interactions can effectively regulate chronic inflammatory conditions. Platelet extracellular vesicles play a prominent role in thrombosis. In this review, we provide an overview of the molecules associated with platelet-cell interaction and the role of platelet extracellular vesicles in cardiovascular disorders and coronavirus disease 2019, which has posed a significant threat to global health due to infection with severe acute respiratory syndrome coronavirus 2. In addition to recruiting leukocytes to resolve inflammation associated with inflammatory diseases, such as coronavirus disease 2019, nutrients may also play a significant role in human metabolism.

13.
Int J Mol Sci ; 23(18)2022 Sep 07.
Article in English | MEDLINE | ID: covidwho-2010122

ABSTRACT

Inhibition of inflammatory responses from the spike glycoprotein of SARS-CoV-2 (Spike) by targeting NLRP3 inflammasome has recently been developed as an alternative form of supportive therapy besides the traditional anti-viral approaches. Clerodendrum petasites S. Moore (C. petasites) is a Thai traditional medicinal plant possessing antipyretic and anti-inflammatory activities. In this study, C. petasites ethanolic root extract (CpEE) underwent solvent-partitioned extraction to obtain the ethyl acetate fraction of C. petasites (CpEA). Subsequently, C. petasites extracts were determined for the flavonoid contents and anti-inflammatory properties against spike induction in the A549 lung cells. According to the HPLC results, CpEA significantly contained higher amounts of hesperidin and hesperetin flavonoids than CpEE (p < 0.05). A549 cells were then pre-treated with either C. petasites extracts or its active flavonoids and were primed with 100 ng/mL of spike S1 subunit (Spike S1) and determined for the anti-inflammatory properties. The results indicate that CpEA (compared with CpEE) and hesperetin (compared with hesperidin) exhibited greater anti-inflammatory properties upon Spike S1 induction through a significant reduction in IL-6, IL-1ß, and IL-18 cytokine releases in A549 cells culture supernatant (p < 0.05). Additionally, CpEA and hesperetin significantly inhibited the Spike S1-induced inflammatory gene expressions (NLRP3, IL-1ß, and IL-18, p < 0.05). Mechanistically, CpEA and hesperetin attenuated inflammasome machinery protein expressions (NLRP3, ASC, and Caspase-1), as well as inactivated the Akt/MAPK/AP-1 pathway. Overall, our findings could provide scientific-based evidence to support the use of C. petasites and hesperetin in the development of supportive therapies for the prevention of COVID-19-related chronic inflammation.


Subject(s)
Antipyretics , COVID-19 , Clerodendrum , Hesperidin , Petasites , A549 Cells , Anti-Inflammatory Agents/pharmacology , COVID-19/drug therapy , Caspase 1/metabolism , Clerodendrum/metabolism , Cytokines/metabolism , Flavonoids/pharmacology , Hesperidin/pharmacology , Humans , Inflammasomes/metabolism , Interleukin-18 , Interleukin-6 , Lung/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Plant Extracts/pharmacology , Proto-Oncogene Proteins c-akt , SARS-CoV-2 , Solvents , Spike Glycoprotein, Coronavirus , Transcription Factor AP-1
14.
Frontiers in Cardiovascular Medicine ; 9, 2022.
Article in English | EMBASE | ID: covidwho-2005852

ABSTRACT

Prolonged critical care stays commonly follow trauma, severe burn injury, sepsis, ARDS, and complications of major surgery. Although patients leave critical care following homeostatic recovery, significant additional diseases affect these patients during and beyond the convalescent phase. New cardiovascular and renal disease is commonly seen and roughly one third of all deaths in the year following discharge from critical care may come from this cluster of diseases. During prolonged critical care stays, the immunometabolic, inflammatory and neurohumoral response to severe illness in conjunction with resuscitative treatments primes the immune system and parenchymal tissues to develop a long-lived pro-inflammatory and immunosenescent state. This state is perpetuated by persistent Toll-like receptor signaling, free radical mediated isolevuglandin protein adduct formation and presentation by antigen presenting cells, abnormal circulating HDL and LDL isoforms, redox and metabolite mediated epigenetic reprogramming of the innate immune arm (trained immunity), and the development of immunosenescence through T-cell exhaustion/anergy through epigenetic modification of the T-cell genome. Under this state, tissue remodeling in the vascular, cardiac, and renal parenchymal beds occurs through the activation of pro-fibrotic cellular signaling pathways, causing vascular dysfunction and atherosclerosis, adverse cardiac remodeling and dysfunction, and proteinuria and accelerated chronic kidney disease.

15.
Journal of Cystic Fibrosis ; 21:S65, 2022.
Article in English | EMBASE | ID: covidwho-1996771

ABSTRACT

Objectives: People with CF (PwCF) are at increased risk of respiratory infections and chronic inflammation.We sought to determine whether the inflammatory response is different in nasal epithelium of PwCF compared to healthy volunteers (HV). Since Interferons can increase ACE2 expression, a protein required for SARS-CoV-2 entry,we focused our analysis on the the focusing on the interferon-response signature. Methods: We reanalysed nasal curettage sample bulk RNA-seq signatures of pilot and validation datasets for which the study methods and demographics of the recruited cohort have already been reported. For this analysis, we performed in-silico deconvolution of bulk RNA-seq data using publicly available single-cell RNA-seq data from nasal epitheliumas a reference to determine the abundance of the specific cell types in each sample. Results: Hierarchical clustering of the pilot and validation cohorts revealed 3 clusters. Analysis of the larger validation cohort revealed that Cluster A included HV (11 out of 11 subjects) and both homozygous (7 out of 13 subjects) and heterozygous (3 out of 10 subjects) PwCF. Subject cluster A was characterised by increased expression of genes related to secretory and ciliated epithelial cells, whereas Clusters B and C contained both homozygous and heterozygous PwCF only and were characterised by genes restricted to neutrophils and involved in immune responses. We then compared samples from cluster A that contained samples from HV (n = 11), PwCF homozygous (n = 7) and heterozygous (n = 3) for F508del. This analysis identified 379 genes upregulated in HV and 146 genes upregulated in PwCF homozygous for F508del and only 44 and 6 genes upregulated in HV and PwCF heterozygous for F508del, respectively (FDR q < 0.05). ACE2, TMPRS2 or other interferon-response genes were not deferentially expressed in either comparison of cluster A. Conclusion: PwCF do not have higher expression of interferon-response genes in nasal epithelial cells

16.
Journal of General Internal Medicine ; 37:S468, 2022.
Article in English | EMBASE | ID: covidwho-1995805

ABSTRACT

CASE: A 59-year-old Mexican-American man with hypertension and type II diabetes (Hemoglobin A1c 11.5) was admitted for sepsis and Acute Respiratory Distress Syndrome secondary to COVID-19 pneumonia. He was ventilator- dependent for 66 days. His clinical course was complicated by acute renal failure requiring hemodialysis, pulmonary embolism, and recurrent ventilator-associated bacterial pneumonia. He was discharged to a long-term acute care center four months after his initial presentation, but was readmitted two weeks later for abdominal pain and fever. CT abdomen revealed diffuse mesenteric nodular stranding and pelvic ascites concerning for peritoneal carcinomatosis. Biopsy of an omental nodule, however, showed necrotizing granulomatous inflammation and no malignant cells. No cultures were sent from the initial biopsy, so repeat sampling was performed and culture was positive for Mycobacterium tuberculosis complex. Treatment for active tuberculosis was initiated with subsequent recovery. IMPACT/DISCUSSION: Initial infection by tuberculosis occurs in the lungs, where alveolar macrophages encounter and phagocytose the bacteria. The macrophages initiate a cytokine response and recruit lymphocytes to form a granuloma, which segregates the infection within the host. The granuloma is then perpetually maintained by an ongoing immune response that is driven by monocytes and CD-4 T cells. Reactivation of tuberculosis occurs when the ongoing immune response is disrupted. Sepsis has profound and complex effects on the immune system, including marked inhibition of lymphocyte proliferation that leads to reduced levels of B cells, CD-4 T cells, and follicular dendritic cells. Signaling pathways are disrupted without these lymphocytes, which then leads to the dysfunction of the remaining leukocytes. Further, critically ill patients often suffer from post-intensive care unit syndrome. This syndrome is marked by persistent inflammation, which prompts an immunosuppressive response that suppresses T-cell function and leads to T-cell apoptosis. Both sepsis and post-intensive care unit syndrome predispose patients to opportunistic infection by attenuation of the usual immune response. In this particular case, the specific loss of T-cell function in both syndromes allowed this patient's latent tuberculosis to reactivate several months after his initial presentation with sepsis from COVID-19 pneumonia. This case highlights the importance of maintaining a high index of suspicion for opportunistic infection after critical illness. CONCLUSION: Sepsis and post-intensive care unit syndrome disrupted this patient's ability to maintain the immune responses that prevent the progression of latent tuberculosis infection. The diagnosis was delayed due to a lack of awareness of the profound immunosuppression that accompanies and follows critical illness. Providers must recognize these syndromes and the impact they have on immunity in order to diagnose and treat opportunistic infections in a timely manner.

17.
Clin Exp Immunol ; 2022 Aug 12.
Article in English | MEDLINE | ID: covidwho-1992119

ABSTRACT

Obesity increases the risk of type 2 diabetes mellitus, cardiovascular disease, fatty liver disease, and cancer. It is also linked with more severe complications from infections, including COVID-19, and poor vaccine responses. Chronic, low-grade inflammation and associated immune perturbations play an important role in determining morbidity in people living with obesity. The contribution of B cells to immune dysregulation and meta-inflammation associated with obesity has been documented by studies over the past decade. With a focus on human studies, here we consolidate the observations demonstrating that there is altered B cell subset composition, differentiation, and function both systemically and in the adipose tissue of individuals living with obesity. Finally, we discuss the potential factors that drive B cell dysfunction in obesity and propose a model by which altered B cell subset composition in obesity underlies dysfunctional B cell responses to novel pathogens.

18.
Cancer Research ; 82(12), 2022.
Article in English | EMBASE | ID: covidwho-1986479

ABSTRACT

Background: Single nucleotide polymorphisms (SNPs) in IL-6, IL-1β, and IL-10 genes have been reported to impact infectious disease outcomes and are associated with altered emotional states. High levels of these cytokines, which have a role in regulating inflammation, have been detected among individuals with severe COVID-19 disease. The objective of this study was to examine if proinflammatory SNPs in the promoter region of IL-6, IL-1β, and IL-10 genes are associated with more severe COVID-19 disease and/or increased anxiety/stress levels in response to pandemicassociated stressors in a vulnerable Hispanic population that is part of the Puerto Rico Colorectal Cancer Registry. Methods: TaqMan® SNP Genotyping Assays (ThermoFisher Scientific) for IL-1β (rs1143627), IL-6 (rs1800795), and IL-10 (rs1800871) were performed according to the manufacturer's recommendations in individuals between the ages of 21 to 75 (n=136). We assessed their anxiety and stress levels using the Generalized Anxiety Disorder Questionnaire (GAD-7) and the Perceived Stress Scale (PSS). Of these individuals, we evaluated those that had been previously infected with COVID-19 (n=38) for their symptom severity through a questionnaire. Chi-Square tests and Multivariate Logistic Regressions were used to calculate associations and ORs. Results: Preliminary analysis showed an association between having the homozygous IL-1β proinflammatory SNP and reporting fever as a symptom (OR=2.50, p-value=0.05). Individuals with the homozygous IL-10 pro-inflammatory SNP had higher odds of reporting difficulty breathing (OR= 4.51, p-value = 0.02), shortness of breath (OR=7.82, p-value=0.006), and fatigue as symptoms (OR=4.43, p-value=0.020. Further analysis also showed an association between having the homozygous IL-10 pro-inflammatory SNP and reporting at least 1 severe COVID-19 symptom (OR=3.38, p-value=0.046). Those with the homozygous or heterozygous IL-6 pro-inflammatory allele were less likely to report higher anxiety levels than those with the wild-type allele (OR=0.1447, p-value=0.04). We also observed that individuals between the ages of 21 to 49 were more likely to report changes in diet (OR=1.65, p-value=0.059) and constantly disinfecting as a pandemic-related stressor (OR=1.87, p-value=0.04) compared to individuals between the ages of 50 to 79. Conclusions: Pro-inflammatory IL-1β and IL-10 SNPs were associated with reporting fever and more severe symptoms of COVID-19, respectively. Data analysis using a larger sample size is warranted and is currently underway. Studies focused on examining that factors that contribute to more severe COVID-19 symptoms and how pandemic-associated stressors promote higher inflammation levels as a result of increased stress/anxiety are needed to fully understand the longterm effects the pandemic on public health, including possible increases in cancer incidence due to chronic inflammation.

19.
Int J Mol Sci ; 23(14)2022 Jul 21.
Article in English | MEDLINE | ID: covidwho-1958594

ABSTRACT

Mesenchymal stem cells (MSCs) play a critical role in response to stress such as infection. They initiate the removal of cell debris, exert major immunoregulatory activities, control pathogens, and lead to a remodeling/scarring phase. Thus, host-derived 'danger' factors released from damaged/infected cells (called alarmins, e.g., HMGB1, ATP, DNA) as well as pathogen-associated molecular patterns (LPS, single strand RNA) can activate MSCs located in the parenchyma and around vessels to upregulate the expression of growth factors and chemoattractant molecules that influence immune cell recruitment and stem cell mobilization. MSC, in an ultimate contribution to tissue repair, may also directly trans- or de-differentiate into specific cellular phenotypes such as osteoblasts, chondrocytes, lipofibroblasts, myofibroblasts, Schwann cells, and they may somehow recapitulate their neural crest embryonic origin. Failure to terminate such repair processes induces pathological scarring, termed fibrosis, or vascular calcification. Interestingly, many viruses and particularly those associated to chronic infection and inflammation may hijack and polarize MSC's immune regulatory activities. Several reports argue that MSC may constitute immune privileged sanctuaries for viruses and contributing to long-lasting effects posing infectious challenges, such as viruses rebounding in immunocompromised patients or following regenerative medicine therapies using MSC. We will herein review the capacity of several viruses not only to infect but also to polarize directly or indirectly the functions of MSC (immunoregulation, differentiation potential, and tissue repair) in clinical settings.


Subject(s)
Mesenchymal Stem Cells , Viruses , Cell Differentiation , Chondrocytes/metabolism , Cicatrix/metabolism , Humans , Mesenchymal Stem Cells/metabolism
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