scholarly journals Macrophage activation in obese type 2 diabetes: an enhanced risk for COVID-19 and Acute Respiratory Distress Syndrome?

2020 ◽  
Author(s):  
Abu Moin ◽  
Thozhukat Sathyapalan ◽  
Ilhame Diboun ◽  
Stephen Atkin ◽  
Alexandra Butler
Keyword(s):  
Type 2 Diabetes ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Macrophage Activation ◽  
Distress Syndrome ◽  
Serum Glucose ◽  
M2 Macrophage ◽  
Activation Markers ◽  
M1 Macrophage

Abstract Objective Hyperactivation of the immune system through obesity and diabetes may enhance infection severity complicated by Acute Respiratory Distress Syndrome (ARDS), the hallmark of severe COVID-19 disease. Objectives: to determine the circulatory biomarkers for macrophage activation at baseline and after serum glucose normalization in obese type 2 diabetes (OT2D) subjects.Methods A case-controlled interventional pilot study in OT2D (n=23) and control subjects (n=23). Subjects underwent hyperinsulinemic clamp normalizing serum glucose. Plasma macrophage-related proteins were determined using Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement at baseline (control and OT2D subjects) and after 1-hour of insulin clamp (OT2D subjects only).Results. Basal M1 macrophage activation was characterized by elevated levels of M1 macrophage-specific surface proteins, CD80 and CD38, and cytokines or chemokines (CXCL1, CXCL5, RANTES) released by activated M1 macrophages. Two potent M1 macrophage activation markers CXCL9 and CXCL10 were decreased in OT2D. Activated M2 macrophages were characterized by elevated levels of plasma CD163, TFGβ-1, MMP7 and MMP9 in OT2D. Conventional mediators of both M1 and M2 macrophage activation markers (IFN-γ, IL-4, IL-13) were not altered. No changes were observed in plasma levels of M1/M2 macrophage activation markers in OT2D in response to acute normalization of glycemia.Conclusion In the basal state, macrophage activation markers are elevated, and these reflect the expression of circulatory cytokines, chemokines, growth factors and matrix metalloproteinases in obese individuals with type 2 diabetes, that were not changed by glucose normalisation. These differences may predispose the diabetic individuals to ARDS reflecting in increased COVID-19 disease severity.

scholarly journals Macrophage activation in obese type 2 diabetes: an enhanced risk for COVID-19 and Acute Respiratory Distress Syndrome?

2020 ◽  
Author(s):  
Abu Moin ◽  
Thozhukat Sathyapalan ◽  
Ilhame Diboun ◽  
Stephen Atkin ◽  
Alexandra Butler
Keyword(s):  
Type 2 Diabetes ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Macrophage Activation ◽  
Distress Syndrome ◽  
Serum Glucose ◽  
M2 Macrophage ◽  
Activation Markers ◽  
M1 Macrophage

Abstract Objective Hyperactivation of the immune system through obesity and diabetes may enhance infection severity complicated by Acute Respiratory Distress Syndrome (ARDS), the hallmark of severe COVID-19 disease. Objectives: to determine the circulatory biomarkers for macrophage activation at baseline and after serum glucose normalization in obese type 2 diabetes (OT2D) subjects.Methods A case-controlled interventional pilot study in OT2D (n=23) and control subjects (n=23). Subjects underwent hyperinsulinemic clamp normalizing serum glucose. Plasma macrophage-related proteins were determined using Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement at baseline (control and OT2D subjects) and after 1-hour of insulin clamp (OT2D subjects only).Results. Basal M1 macrophage activation was characterized by elevated levels of M1 macrophage-specific surface proteins, CD80 and CD38, and cytokines or chemokines (CXCL1, CXCL5, RANTES) released by activated M1 macrophages. Two potent M1 macrophage activation markers CXCL9 and CXCL10 were decreased in OT2D. Activated M2 macrophages were characterized by elevated levels of plasma CD163, TFGβ-1, MMP7 and MMP9 in OT2D. Conventional mediators of both M1 and M2 macrophage activation markers (IFN-γ, IL-4, IL-13) were not altered. No changes were observed in plasma levels of M1/M2 macrophage activation markers in OT2D in response to acute normalization of glycemia.Conclusion In the basal state, macrophage activation markers are elevated, and these reflect the expression of circulatory cytokines, chemokines, growth factors and matrix metalloproteinases in obese individuals with type 2 diabetes, that were not changed by glucose normalisation. These differences may predispose the diabetic individuals to ARDS reflecting in increased COVID-19 disease severity.

scholarly journals Identification of macrophage activation-related biomarkers in obese type 2 diabetes that may be indicative of enhanced respiratory risk in COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abu Saleh Md Moin ◽  
Thozhukat Sathyapalan ◽  
Ilhame Diboun ◽  
Stephen L. Atkin ◽  
Alexandra E. Butler
Keyword(s):  
Type 2 Diabetes ◽  
Macrophage Activation ◽  
Serum Glucose ◽  
Surface Proteins ◽  
M2 Macrophage ◽  
Activation Markers ◽  
Obesity And Diabetes ◽  
M1 Macrophage ◽  
Glucose Plasma

AbstractHyperactivation of the immune system through obesity and diabetes may enhance infection severity complicated by Acute Respiratory Distress Syndrome (ARDS). The objective was to determine the circulatory biomarkers for macrophage activation at baseline and after serum glucose normalization in obese type 2 diabetes (OT2D) subjects. A case-controlled interventional pilot study in OT2D (n = 23) and control subjects (n = 23). OT2D subjects underwent hyperinsulinemic clamp to normalize serum glucose. Plasma macrophage-related proteins were determined using Slow Off-rate Modified Aptamer-scan plasma protein measurement at baseline (control and OT2D subjects) and after 1-h of insulin clamp (OT2D subjects only). Basal M1 macrophage activation was characterized by elevated levels of M1 macrophage-specific surface proteins, CD80 and CD38, and cytokines or chemokines (CXCL1, CXCL5, RANTES) released by activated M1 macrophages. Two potent M1 macrophage activation markers, CXCL9 and CXCL10, were decreased in OT2D. Activated M2 macrophages were characterized by elevated levels of plasma CD163, TFGβ-1, MMP7 and MMP9 in OT2D. Conventional mediators of both M1 and M2 macrophage activation markers (IFN-γ, IL-4, IL-13) were not altered. No changes were observed in plasma levels of M1/M2 macrophage activation markers in OT2D in response to acute normalization of glycemia. In the basal state, macrophage activation markers are elevated, and these reflect the expression of circulatory cytokines, chemokines, growth factors and matrix metalloproteinases in obese individuals with type 2 diabetes, that were not changed by glucose normalisation. These differences could potentially predispose diabetic individuals to increased infection severity complicated by ARDS. Clinical trial reg. no: NCT03102801; registration date April 6, 2017.

scholarly journals A Case of Concomitant COVID-19 Infection-Induced Acute Respiratory Distress Syndrome and Diabetic Ketoacidosis: Another Challenge in Fluid Management

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A357-A357
Author(s):  
Panadeekarn Panjawatanan ◽  
Samir Jha ◽  
Joseph Hughes ◽  
Erik Riesenfeld
Keyword(s):  
Type 2 Diabetes ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Diabetic Ketoacidosis ◽  
Distress Syndrome ◽  
Insulin Degludec ◽  
Intravenous Insulin ◽  
Sliding Scale

Abstract Background: Coronavirus Disease 2019 (COVID-19) has been announced as a pandemic worldwide. The respiratory tract is a target organ-system which can result in serious complications like acute respiratory distress syndrome (ARDS). Management of this condition is more challenging in diabetes who developed diabetic ketoacidosis (DKA). Clinical Case: We report a case of a 59-year-old male who presented with 4 days of productive cough with blood-tinged sputum, shortness of breath, and chills. Patient had decreased oral intake and had not been compliant with his medication. He had underlying disease significant for type 2 diabetes, essential hypertension, obesity (BMI 32 kg/m2), history of pancreatitis and diabetic ketoacidosis. His diabetes medications included insulin degludec 126 units with insulin lispro sliding scale, dulaglutide, metformin, and sitagliptin. On examination, the patient was lethargic. Initial vital signs included a temperature of 36.8°C, respiratory rate 24/min, heart rate 65 bpm, BP 140/67 mmHg, and oxygen saturation 91% on room air. Lung auscultation revealed bilateral widespread crackles. Laboratory was significant for glucose 387 mg/dL (70–139), pH 7.25 (7.35-7.28), anion gap 15.8 mEq/L (6–14) and concurrent normal gap acidosis, urine ketones 15 mg/dL (negative), and LDH 325 U/L (140–171). An initial chest x-ray showed bilateral peripheral pulmonary infiltrates. Workup was negative for influenza, pneumococcus, and legionella. The patient was subsequently intubated on the first day for worsening hypoxia due to severe ARDS (PaO2/FiO2 ratio of 71). He was concomitantly treated for DKA and hypotension with intravenous insulin, initially started at 12 units/hour with subsequent titration down to average of 5 units/hour, fluid resuscitation (approximate 34 ml/kg actual body weight) and, potassium repletion on the first day. On the same day, his hypoxia worsened with an increase in pulmonary infiltrates, so we stopped intravenous fluids and initiated norepinephrine for 24 hours. His mechanical ventilation settings followed ARDS guidelines. Positive COVID-19 was detected from real-time RT-PCR. After maintaining a negative fluid balance, we were able to extubate in 72 hours. Intravenous insulin was continued for 46 hours then was switched to subcutaneous basal-bolus regimen. He was discharged with insulin degludec 100 units with insulin lispro sliding scale, metformin, and sitagliptin. Dulaglutide was held. Conclusion: Type 2 diabetes are rarely affected by DKA but can be found in up to 27% of the cases. There are reports of ARDS as a serious complication in severe DKA in adults and children, yet no data for concomitant DKA and ARDS has been published. We propose that the management of DKA in COVID-19 patients with ARDS may be similar to the paradigm utilized for other volume restriction in patients with congestive heart failure and end-stage renal failure.

scholarly journals CircN4bp1 Facilitates Sepsis-Induced Acute Respiratory Distress Syndrome through Mediating Macrophage Polarization via the miR-138-5p/EZH2 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Dongyang Zhao ◽  
Chunxue Wang ◽  
Xiandong Liu ◽  
Na Liu ◽  
Shougang Zhuang ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Macrophage Activation ◽  
Distress Syndrome ◽  
Rna Binding ◽  
Macrophage Polarization ◽  
Expression Patterns ◽  
Luciferase Reporter ◽  
M1 Macrophage

We recently reported the differential circRNA expression patterns of the pulmonary macrophages in sepsis-induced acute respiratory distress syndrome (ARDS) mice model by microarray analysis. However, their function and hidden molecular mechanism in regulation of macrophage activation and inflammation remain poorly understood. In this study, we found that circN4bp1was overexpressed in PBMC and monocytes, and its expression levels were correlated with a poor prognosis in sepsis induced ARDS patients induced by sepsis. Knockdown of circN4bp1 inhibited the lung injury and improved the long-time survival through blunting the M1 macrophage activation in cecal ligation and puncture- (CLP-) induced ARDS mice. Moreover, bioinformatics analysis predicated a circN4bp1/miR-138-5p ceRNA network, which was confirmed by luciferase reporter assay and RNA binding protein immunoprecipitation (RIP). CircN4bp1 affected macrophage differentiation by binding to miR-138-5p, thus regulating the expression of EZH2 in vivo and ex vivo. Lastly, the m6A level of circN4bp1was found to be elevated in ARDS mice; inhibition of m6A methyltransferase METTL3 blocked this response in vitro. Therefore, circN4bp1 can function as a miR-138-5p sponge for the modulation of macrophage polarization through regulation the expression of EZH2 and may serve as a potential target and/or prognostic marker for ARDS patients following sepsis.

scholarly journals Release of endothelial activation markers in lungs of patients with malaria-associated acute respiratory distress syndrome

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Thao-Thy Pham ◽  
Chuchard Punsawad ◽  
Supattra Glaharn ◽  
Simon F. De Meyer ◽  
Parnpen Viriyavejakul ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Endothelial Activation ◽  
Post Mortem ◽  
Endothelial Lining ◽  
Activation Markers ◽  
Alveolar Oedema ◽  
Alveolar Septa

Abstract Background Malaria-associated acute respiratory distress syndrome (MA-ARDS) is an understudied complication of malaria and is characterized by pulmonary inflammation and disruption of the alveolar-capillary membrane. Its pathogenesis remains poorly understood. Since endothelial activation plays an important role in other malarial complications, the expression of two endothelial activation markers, von Willebrand factor (VWF) and angiopoietin-2 (ANG-2), was investigated in the lungs of patients with MA-ARDS. Methods Post-mortem lung sections of Plasmodium falciparum-infected patients without alveolar oedema (NA), P. falciparum-infected patients with alveolar oedema (MA-ARDS), and uninfected people who died accidentally with no pathological changes to the lungs (CON) were immunohistochemically stained for VWF and ANG-2, and were evaluated with semi-quantitative analysis. Results Alveolar oedematous VWF and ANG-2 and intravascular VWF staining were significantly increased in patients with MA-ARDS versus infected and uninfected control groups. The levels of VWF in the alveolar septa and endothelial lining of large blood vessels of patients with MA-ARDS was significantly decreased compared to controls. ANG-2 expression was increased in the alveolar septa of malaria patients without alveolar oedema versus control patients, while ANG-2+ leukocytes were increased in the alveoli in both infected patient groups. Conclusions This study documents a high level of VWF and ANG-2, two endothelial activation markers in the oedematous alveoli of post-mortem lung sections of Thai patients with MA-ARDS. Decreased detection of VWF in the endothelial lining of blood vessels, in parallel with an increased presence of intravascular VWF staining suggests marked endothelial activation and Weibel–Palade body release in the lungs of patients with MA-ARDS.

scholarly journals The Role of Macrophages in the Pathogenesis of SARS-CoV-2-Associated Acute Respiratory Distress Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna Kosyreva ◽  
Dzhuliia Dzhalilova ◽  
Anastasia Lokhonina ◽  
Polina Vishnyakova ◽  
Timur Fatkhudinov
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Macrophage Activation ◽  
Distress Syndrome ◽  
Innate And Adaptive Immunity ◽  
Cell Therapies ◽  
Coronavirus Infection ◽  
Inflammatory Phenotypes

Macrophages are cells that mediate both innate and adaptive immunity reactions, playing a major role in both physiological and pathological processes. Systemic SARS-CoV-2-associated complications include acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation syndrome, edema, and pneumonia. These are predominantly effects of massive macrophage activation that collectively can be defined as macrophage activation syndrome. In this review we focus on the role of macrophages in COVID-19, as pathogenesis of the new coronavirus infection, especially in cases complicated by ARDS, largely depends on macrophage phenotypes and functionalities. We describe participation of monocytes, monocyte-derived and resident lung macrophages in SARS-CoV-2-associated ARDS and discuss possible utility of cell therapies for its treatment, notably the use of reprogrammed macrophages with stable pro- or anti-inflammatory phenotypes.

scholarly journals Сlinical case of occurrence of myocardial infarction type 2 as a complication of new coronavirus infection

2021 ◽  
Vol 22 (3) ◽  
pp. 65-70
Author(s):  
D. V. Oblavatckii ◽  
S. A. Boldueva ◽  
S. V. Alekseeva ◽  
A. A. Sushkova ◽  
R. R. Mikhailov ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Cardiovascular Events ◽  
Clinical Case ◽  
Distress Syndrome ◽  
Coronavirus Infection

As known, a new coronavirus infection that causes acute respiratory distress syndrome can proceed in severe forms and lead to various complications, including acute cardiovascular events. This article describes a clinical case of the occurrence of acute myocardial infarction in a patient with a confirmed diagnosis of coronavirus infection. A peculiarity of this observation is the pathogenesis of the development of myocardial infarction, which is not directly related to atherothrombosis and differs from the classic type 1 myocardial infarction.

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