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1.
Lancet Respir Med ; 9(5): 533-544, 2021 05.
Article in English | MEDLINE | ID: covidwho-1931217

ABSTRACT

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Cough/etiology , Inflammation/etiology , Nervous System Diseases/etiology , Neuroimmunomodulation , Cough/physiopathology , Humans , Inflammation/physiopathology , Nervous System Diseases/physiopathology , SARS-CoV-2 , Syndrome
2.
Neuropharmacology ; 209: 109023, 2022 05 15.
Article in English | MEDLINE | ID: covidwho-1821424

ABSTRACT

Acute neurological alterations have been associated with SARS-CoV-2 infection. Additionally, it is becoming clear that coronavirus disease 2019 (COVID-19) survivors may experience long-term neurological abnormalities, including cognitive deficits and mood alterations. The mechanisms underlying acute and long-term impacts of COVID-19 in the brain are being actively investigated. Due to the heterogeneous manifestations of neurological outcomes, it is possible that different mechanisms operate following SARS-CoV-2 infection, which may include direct brain infection by SARS-CoV-2, mechanisms resulting from hyperinflammatory systemic disease, or a combination of both. Inflammation is a core feature of COVID-19, and both central and systemic inflammation are known to lead to acute and persistent neurological alterations in other diseases. Here, we review evidence indicating that COVID-19 is associated with neuroinflammation, along with blood-brain barrier dysfunction. Similar neuroinflammatory signatures have been associated with Alzheimer's disease and major depressive disorder. Current evidence demonstrates that patients with pre-existing cognitive and neuropsychiatric deficits show worse outcomes upon infection by SARS-CoV-2 and, conversely, COVID-19 survivors may be at increased risk of developing dementia and mood disorders. Considering the high prevalence of COVID-19 patients that recovered from infection in the world and the alarming projections for the prevalence of dementia and depression, investigation of possible molecular similarities between those diseases may shed light on mechanisms leading to long-term neurological abnormalities in COVID-19 survivors.


Subject(s)
COVID-19/complications , Cognitive Dysfunction/etiology , Depression/etiology , Neuroinflammatory Diseases/physiopathology , Affect/physiology , Blood-Brain Barrier/metabolism , COVID-19/physiopathology , Cognitive Dysfunction/physiopathology , Depression/physiopathology , Humans , Inflammation/physiopathology , SARS-CoV-2 , Virus Diseases/complications
3.
Science ; 374(6571): 1076-1080, 2021 Nov 26.
Article in English | MEDLINE | ID: covidwho-1723462

ABSTRACT

Inflammatory processes that recruit leukocytes to injured or infected tissues are crucial for tissue repair and the elimination of pathogens. However, excessive or chronic inflammation promotes tissue damage and disease, as in arthritis, atherosclerosis, inflammatory bowel disease, and COVID-19. Intracellular constituents released from dying cells are among the stimuli that trigger proinflammatory gene expression programs in innate immune cells. We explore how programmed cell death mechanisms­apoptosis, necroptosis, and pyroptosis­may contribute to inflammatory disease. We discuss inhibition of cell death as a potential therapeutic strategy, focusing on the targets RIPK1 (receptor interacting serine/threonine kinase 1), NLRP3 (NLR family pyrin domain containing 3), and GSDMD (gasdermin D) as important mediators of lytic cell death. We also consider the potential benefits of limiting membrane rupture rather than cell death by targeting NINJ1.


Subject(s)
Apoptosis , Inflammation/physiopathology , Necroptosis , Pyroptosis , Animals , Caspase 8/metabolism , Cell Adhesion Molecules, Neuronal/antagonists & inhibitors , Cell Adhesion Molecules, Neuronal/metabolism , Fas-Associated Death Domain Protein/metabolism , Humans , Inflammasomes/metabolism , Inflammation/drug therapy , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Intracellular Signaling Peptides and Proteins/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Nerve Growth Factors/antagonists & inhibitors , Nerve Growth Factors/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases/deficiency , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism
4.
J Interferon Cytokine Res ; 42(2): 49-61, 2022 02.
Article in English | MEDLINE | ID: covidwho-1692282

ABSTRACT

The interleukin (IL)-1 superfamily of cytokines comprises 11 pro- and anti-inflammatory cytokines, which play essential roles during the immune response. Several pathogenic pathways are initiated by IL-1RL2 (interleukin 1 receptor-like 2) signaling, also known as IL-36R, in the skin, lungs, and gut. IL-36 cytokines promote the secretion of proinflammatory cytokines and chemokines, upregulation of antimicrobial peptides, proliferation mediators, and adhesion molecules on endothelial cells. In addition, the IL-36-IL-1RL2 axis has an essential role against viral infections, including a potential role in COVID-19 pathology. The evidence presented in this review highlights the importance of the axis IL-36-IL-1RL2 in the development of several inflammation-related diseases and the healing process. It suggests that IL-1RL2 ligands have specific roles depending on the tissue or cell source. However, there is still much to discover about this cytokine family, their functions in other organs, and how they accomplish a dual effect in inflammation and healing.


Subject(s)
Inflammation/physiopathology , Receptors, Interleukin-1/physiology , Animals , COVID-19/physiopathology , Cytokine Release Syndrome/physiopathology , Cytokines/physiology , Host-Pathogen Interactions , Humans , Interleukin-1/physiology , Interleukins/classification , Intestines/metabolism , Intestines/pathology , Ligands , Lung/metabolism , Lung/pathology , MAP Kinase Signaling System , Mice , NF-kappa B/metabolism , Protein Domains , Receptors, Interleukin/classification , Receptors, Interleukin-1/agonists , Receptors, Interleukin-1/antagonists & inhibitors , Receptors, Interleukin-1/chemistry , SARS-CoV-2 , Signal Transduction , Skin/metabolism , Skin/pathology
5.
Mol Cell Biochem ; 477(4): 1155-1193, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1653634

ABSTRACT

A growing amount of epidemiological data from multiple countries indicate an increased prevalence of obesity, more importantly central obesity, among hospitalized subjects with COVID-19. This suggests that obesity is a major factor contributing to adverse outcome of the disease. As it is a metabolic disorder with dysregulated immune and endocrine function, it is logical that dysfunctional metabolism contributes to the mechanisms behind obesity being a risk factor for adverse outcome in COVID-19. Emerging data suggest that in obese subjects, (a) the molecular mechanisms of viral entry and spread mediated through ACE2 receptor, a multifunctional host cell protein which links to cellular homeostasis mechanisms, are affected. This includes perturbation of the physiological renin-angiotensin system pathway causing pro-inflammatory and pro-thrombotic challenges (b) existent metabolic overload and ER stress-induced UPR pathway make obese subjects vulnerable to severe COVID-19, (c) host cell response is altered involving reprogramming of metabolism and epigenetic mechanisms involving microRNAs in line with changes in obesity, and (d) adiposopathy with altered endocrine, adipokine, and cytokine profile contributes to altered immune cell metabolism, systemic inflammation, and vascular endothelial dysfunction, exacerbating COVID-19 pathology. In this review, we have examined the available literature on the underlying mechanisms contributing to obesity being a risk for adverse outcome in COVID-19.


Subject(s)
Adiposity/physiology , Body Mass Index , COVID-19/physiopathology , Intra-Abdominal Fat/physiology , Obesity/physiopathology , COVID-19/epidemiology , COVID-19/virology , Cardiovascular Diseases/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Humans , Inflammation/physiopathology , Pandemics , Risk Factors , SARS-CoV-2/physiology
6.
Sci Rep ; 12(1): 1075, 2022 01 20.
Article in English | MEDLINE | ID: covidwho-1642005

ABSTRACT

Inflammatory diseases including COVID-19 are associated with a cytokine storm characterized by high interleukin-6 (IL-6) titers. In particular, while recent studies examined COVID-19 associated arrhythmic risks from cardiac injury and/or from pharmacotherapy such as the combination of azithromycin (AZM) and hydroxychloroquine (HCQ), the role of IL-6 per se in increasing the arrhythmic risk remains poorly understood. The objective is to elucidate the electrophysiological basis of inflammation-associated arrhythmic risk in the presence of AZM and HCQ. IL-6, AZM and HCQ were concomitantly administered to guinea pigs in-vivo and in-vitro. Electrocardiograms, action potentials and ion-currents were analyzed. IL-6 alone or the combination AZM + HCQ induced mild to moderate reduction in heart rate, PR-interval and corrected QT (QTc) in-vivo and in-vitro. Notably, IL-6 alone was more potent than the combination of the two drugs in reducing heart rate, increasing PR-interval and QTc. In addition, the in-vivo or in-vitro combination of IL-6 + AZM + HCQ caused severe bradycardia, conduction abnormalities, QTc prolongation and asystole. These electrocardiographic abnormalities were attenuated in-vivo by tocilizumab (TCZ), a monoclonal antibody against IL-6 receptor, and are due in part to the prolongation of action potential duration and selective inhibition of Na+, Ca2+ and K+ currents. Inflammation confers greater risk for arrhythmia than the drug combination therapy. As such, in the setting of elevated IL-6 during inflammation caution must be taken when co-administering drugs known to predispose to fatal arrhythmias and TCZ could be an important player as a novel anti-arrhythmic agent. Thus, identifying inflammation as a critical culprit is essential for proper management.


Subject(s)
Arrhythmias, Cardiac , Azithromycin/pharmacology , COVID-19 , Hydroxychloroquine/pharmacology , Interleukin-6/metabolism , SARS-CoV-2/metabolism , Animals , Antibodies, Monoclonal, Humanized/pharmacology , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/prevention & control , COVID-19/complications , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/physiopathology , Female , Guinea Pigs , Humans , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/physiopathology , Interleukin-6/antagonists & inhibitors , Male
7.
Hepatol Commun ; 6(2): 255-269, 2022 02.
Article in English | MEDLINE | ID: covidwho-1525435

ABSTRACT

Liver injury, characterized predominantly by elevated aspartate aminotransferase and alanine aminotransferase, is a common feature of coronavirus disease 2019 (COVID-19) symptoms caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Additionally, SARS-CoV-2 infection is associated with acute-on-chronic liver failure in patients with cirrhosis and has a notably elevated mortality in patients with alcohol-related liver disease compared to other etiologies. Direct viral infection of the liver with SARS-CoV-2 remains controversial, and alternative pathophysiologic explanations for its hepatic effects are an area of active investigation. In this review, we discuss the effects of SARS-CoV-2 and the inflammatory environment it creates on endothelial cells and platelets more generally and then with a hepatic focus. In doing this, we present vascular inflammation and thrombosis as a potential mechanism of liver injury and liver-related complications in COVID-19.


Subject(s)
Blood Platelet Disorders/virology , COVID-19/physiopathology , Endothelium, Vascular/virology , Inflammation/virology , Liver Diseases/virology , Thrombosis/virology , Blood Platelet Disorders/immunology , Blood Platelet Disorders/physiopathology , COVID-19/immunology , Endothelium, Vascular/immunology , Endothelium, Vascular/physiopathology , Humans , Inflammation/immunology , Inflammation/physiopathology , Liver Diseases/immunology , Liver Diseases/physiopathology , Thrombosis/immunology , Thrombosis/physiopathology
8.
Indian J Pathol Microbiol ; 64(4): 735-740, 2021.
Article in English | MEDLINE | ID: covidwho-1485280

ABSTRACT

BACKGROUND: COVID-19 is a pandemic viral disease that has affected the Indian population very badly with more than 8.46 million cases and > 0.125 million deaths. AIM: Primary objective of the study is to establish the role of hematological, coagulation and inflammatory biomarkers in early identification of clinically severe covid-19 cases. MATERIALS AND METHODS: This study was conducted from July 2020 to August 2020 at a dedicated COVID-19 referral hospital in central India. Only RT-PCR confirmed COVID-19 positive 300 cases admitted in the hospital were included in this study. Based on the clinical assessment, patients were categorised as mild, moderate, and severe groups as per ICMR guidelines. Blood samples of all cases were tested for haematological, coagulation and inflammatory biomarkers and mean values were compared among the three groups of patients. RESULTS: 46% patients belonged to >60 years of age group. Hematological parameters like total leukocyte count, absolute neutrophil count, Neutrophil: Lymphocyte ratio, Platelet: Lymphocyte ratio significantly increased with lymphocytopenia (P=0.001). Coagulation profile(D-dimer and PT) and inflammatory biomarkers like CRP, LDH, ferritin, procalcitonin and NT- Pro BNP, all were significantly increased with severity of patients(p=0.001). ROC plotted for all the parameters between severe v/s non-severe cases showed that CRP, LDH and D-dimer had a good discriminative precision with AUC >0.8. CONCLUSION: We suggest that biochemical markers like CRP, LDH and D-dimer can be used as a screening tool to differentiate severe patients from non-severe patients of Covid-19 disease in order to identify severe disease at early stage for optimal utilization of resources & reducing further morbidity & mortality.


Subject(s)
Biomarkers/blood , Blood Coagulation/physiology , COVID-19/physiopathology , Early Diagnosis , Inflammation/blood , Inflammation/physiopathology , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Female , Humans , India , Male , Middle Aged , Predictive Value of Tests , Prognosis , SARS-CoV-2
9.
CNS Neurosci Ther ; 27(12): 1433-1436, 2021 12.
Article in English | MEDLINE | ID: covidwho-1462759

ABSTRACT

After almost a year of COVID-19, the chronic long-COVID syndrome has been recognized as an entity in 2021. The patients with the long-COVID are presenting with ominous neurological deficits that with time are becoming persistent and are causing disabilities in the affected individuals. The mechanisms underlying the neurological syndrome in long-COVID have remained obscure and need to be actively researched to find a resolution for the patients with long-COVID. Here, the factors like site of viral load, the differential immune response, neurodegenerative changes, and inflammation as possible causative factors are debated to understand and investigate the pathogenesis of neuro-COVID in long-COVID syndrome.


Subject(s)
COVID-19/complications , Nervous System Diseases/physiopathology , COVID-19/physiopathology , COVID-19/virology , Humans , Inflammation/etiology , Inflammation/physiopathology , Nervous System Diseases/etiology , Neurodegenerative Diseases/etiology , Neurodegenerative Diseases/physiopathology , Viral Load
10.
Int J Immunopathol Pharmacol ; 35: 20587384211048026, 2021.
Article in English | MEDLINE | ID: covidwho-1440891

ABSTRACT

COVID-19 is a highly heterogeneous and complex medical disorder; indeed, severe COVID-19 is probably amongst the most complex of medical conditions known to medical science. While enormous strides have been made in understanding the molecular pathways involved in patients infected with coronaviruses an overarching and comprehensive understanding of the pathogenesis of COVID-19 is lacking. Such an understanding is essential in the formulation of effective prophylactic and treatment strategies. Based on clinical, proteomic, and genomic studies as well as autopsy data severe COVID-19 disease can be considered to be the connection of three basic pathologic processes, namely a pulmonary macrophage activation syndrome with uncontrolled inflammation, a complement-mediated endothelialitis together with a procoagulant state with a thrombotic microangiopathy. In addition, platelet activation with the release of serotonin and the activation and degranulation of mast cells contributes to the hyper-inflammatory state. Auto-antibodies have been demonstrated in a large number of hospitalized patients which adds to the end-organ damage and pro-thrombotic state. This paper provides a clinical overview of the major pathogenetic mechanism leading to severe COVID-19 disease.


Subject(s)
COVID-19/virology , SARS-CoV-2/pathogenicity , COVID-19/blood , COVID-19/immunology , COVID-19/physiopathology , Complement Activation , Complement System Proteins/metabolism , Cytokines/blood , Disease Progression , Host-Pathogen Interactions , Humans , Inflammation/blood , Inflammation/immunology , Inflammation/physiopathology , Inflammation/virology , Inflammation Mediators/blood , Macrophage Activation Syndrome/blood , Macrophage Activation Syndrome/immunology , Macrophage Activation Syndrome/physiopathology , Macrophage Activation Syndrome/virology , Platelet Activation , SARS-CoV-2/immunology , Serotonin/blood , Severity of Illness Index , Thrombotic Microangiopathies/blood , Thrombotic Microangiopathies/immunology , Thrombotic Microangiopathies/physiopathology , Thrombotic Microangiopathies/virology
12.
Proc Natl Acad Sci U S A ; 118(38)2021 09 21.
Article in English | MEDLINE | ID: covidwho-1392993

ABSTRACT

COVID-19 induces a robust, extended inflammatory "cytokine storm" that contributes to an increased morbidity and mortality, particularly in patients with type 2 diabetes (T2D). Macrophages are a key innate immune cell population responsible for the cytokine storm that has been shown, in T2D, to promote excess inflammation in response to infection. Using peripheral monocytes and sera from human patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a murine hepatitis coronavirus (MHV-A59) (an established murine model of SARS), we identified that coronavirus induces an increased Mφ-mediated inflammatory response due to a coronavirus-induced decrease in the histone methyltransferase, SETDB2. This decrease in SETDB2 upon coronavirus infection results in a decrease of the repressive trimethylation of histone 3 lysine 9 (H3K9me3) at NFkB binding sites on inflammatory gene promoters, effectively increasing inflammation. Mφs isolated from mice with a myeloid-specific deletion of SETDB2 displayed increased pathologic inflammation following coronavirus infection. Further, IFNß directly regulates SETDB2 in Mφs via JaK1/STAT3 signaling, as blockade of this pathway altered SETDB2 and the inflammatory response to coronavirus infection. Importantly, we also found that loss of SETDB2 mediates an increased inflammatory response in diabetic Mϕs in response to coronavirus infection. Treatment of coronavirus-infected diabetic Mφs with IFNß reversed the inflammatory cytokine production via up-regulation of SETDB2/H3K9me3 on inflammatory gene promoters. Together, these results describe a potential mechanism for the increased Mφ-mediated cytokine storm in patients with T2D in response to COVID-19 and suggest that therapeutic targeting of the IFNß/SETDB2 axis in T2D patients may decrease pathologic inflammation associated with COVID-19.


Subject(s)
Coronavirus/metabolism , Diabetes Mellitus, Type 2/metabolism , Histone-Lysine N-Methyltransferase/metabolism , Inflammation Mediators/metabolism , Inflammation/virology , Macrophages/metabolism , Animals , COVID-19/immunology , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Cytokine Release Syndrome , Cytokines/metabolism , Diabetes Mellitus, Type 2/genetics , Female , Histone-Lysine N-Methyltransferase/genetics , Humans , Inflammation/metabolism , Inflammation/physiopathology , Male , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , SARS-CoV-2/metabolism , Signal Transduction
13.
Cells ; 10(7)2021 07 20.
Article in English | MEDLINE | ID: covidwho-1389305

ABSTRACT

Microglia are the resident immune cells of the central nervous system contributing substantially to health and disease. There is increasing evidence that inflammatory microglia may induce or accelerate brain aging, by interfering with physiological repair and remodeling processes. Many viral infections affect the brain and interfere with microglia functions, including human immune deficiency virus, flaviviruses, SARS-CoV-2, influenza, and human herpes viruses. Especially chronic viral infections causing low-grade neuroinflammation may contribute to brain aging. This review elucidates the potential role of various neurotropic viruses in microglia-driven neurocognitive deficiencies and possibly accelerated brain aging.


Subject(s)
Aging , Brain/physiopathology , Inflammation/physiopathology , Microglia/virology , Virus Diseases/physiopathology , Animals , Brain/immunology , Brain/virology , COVID-19/immunology , COVID-19/physiopathology , COVID-19/virology , Humans , Inflammation/immunology , Inflammation/virology , Microglia/immunology , Microglia/pathology , SARS-CoV-2/physiology , Virus Diseases/immunology , Virus Diseases/virology
14.
Curr Neurovasc Res ; 18(1): 162-168, 2021.
Article in English | MEDLINE | ID: covidwho-1374189

ABSTRACT

BACKGROUND: Robust evidence has described that Parkinson´s disease (PD) is associated with an increased risk for developing epileptic seizures. In fact, an interplay between PD and epilepsy has been of interest for many years. An emerging hypothesis is that inflammation could link both diseases. OBJECTIVE: Bearing in mind the experience of our group in the field of Ca2+/cAMP signalling pathways, this article discussed, beyond inflammation, the role of these signalling pathways in this link between PD and epilepsy. METHODS: Publications involving Ca2+/cAMP signalling pathways, PD, and epilepsy (alone or combined) were collected by searching PubMed and EMBASE. RESULTS: The comprehension of the interplay between PD and epilepsy could improve the drug therapy. In addition, a Ca2+ signalling dyshomeostasis due to Coronavirus disease 2019 (COVID-19), an emerging and rapidly evolving situation, has been reported. CONCLUSION: Thus, this article also debated recent findings about therapeutics involving Ca2+ channel blockers for preventing Ca2+ signalling dyshomeostasis due to COVID-19, including the correlation among COVID-19, epilepsy, and PD.


Subject(s)
Calcium Signaling , Cyclic AMP , Epilepsy/complications , Inflammation/complications , Parkinson Disease/complications , Signal Transduction , COVID-19/complications , Calcium Channel Blockers/therapeutic use , Epilepsy/physiopathology , Humans , Inflammation/physiopathology , Parkinson Disease/physiopathology
15.
Biomed Res Int ; 2021: 9987931, 2021.
Article in English | MEDLINE | ID: covidwho-1367496

ABSTRACT

OBJECTIVE: Respiratory failure is the leading cause of mortality in COVID-19 patients, characterized by a generalized disbalance of inflammation. The aim of this study was to investigate the relationship between immune-inflammatory index and mortality in PSI IV-V patients with COVID-19. METHODS: We retrospectively reviewed the medical records of COVID-19 patients from Feb. to Apr. 2020 in the Zhongfa Xincheng Branch of Tongji Hospital, Wuhan, China. Patients who presented high severity of COVID-19-related pneumonia were enrolled for further analysis according to the Pneumonia Severity Index (PSI) tool. RESULTS: A total of 101 patients diagnosed with COVID-19 were identified at initial research. The survival analysis revealed that mortality of the PSI IV-V cohort was significantly higher than the PSI I-III group (p = 0.0003). The overall mortality in PSI IV-V patients was 32.1% (9/28). The fatal cases of the PSI IV-V group had a higher level of procalcitonin (p = 0.022) and neutrophil-to-lymphocyte ratio (p = 0.033) compared with the survivors. Procalcitonin was the most sensitive predictor of mortality for the severe COVID-19 population with area under receiver operating characteristic curve of 0.78, higher than the neutrophil-to-lymphocyte ratio (0.75) and total lymphocyte (0.68) and neutrophil (0.67) counts. CONCLUSION: Procalcitonin and neutrophil-to-lymphocyte ratio may potentially be effective predictors for mortality in PSI IV-V patients with COVID-19. Increased procalcitonin and neutrophil-to-lymphocyte ratio were associated with greater risk of mortality.


Subject(s)
COVID-19/immunology , COVID-19/physiopathology , Pandemics , SARS-CoV-2 , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/mortality , China/epidemiology , Cohort Studies , Female , Humans , Inflammation/immunology , Inflammation/physiopathology , Lymphocytes/immunology , Male , Middle Aged , Neutrophils/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Procalcitonin/blood , Prognosis , Retrospective Studies , Risk Factors , Severity of Illness Index , Survival Analysis
16.
Biol Aujourdhui ; 215(1-2): 63-72, 2021.
Article in French | MEDLINE | ID: covidwho-1358360

ABSTRACT

Obesity is considered a pandemic responsible for millions of deaths worldwide for many years. At the end of 2019, the Coronavirus disease 2019 (COVID-19) appeared, causing the death of more than a million people in less than a year. Numerous studies suggest that obesity could be defined as key to the onset of severe forms of this emerging disease. Indeed, SARS-CoV2 infects the host by binding to ACE2 receptors present on the surface of the cells and causes excessive secretion of pro-inflammatory cytokines including IL-1, IL-6 and TNF-α, which lead to developing acute respiratory distress syndrome (ARDS). It therefore seems essential to make up effective preventive strategies to protect this part of the population from the risk of developing a severe form of COVID-19. The ketogenic diet, which is low in sugars and high in fat, has interesting properties, both in the fight against obesity but also against severe infections. This article focuses on the latest scientific advances that make it possible to consider the ketogenic diet as a preventive strategy that simultaneously reduces the development of obesity while strengthening the immune system, two key actions in the fight against SARS-CoV2 infections and severe forms of COVID-19.


TITLE: Obésité, inflammation et COVID-19 : intérêt préventif de l'alimentation cétogène ? ABSTRACT: L'obésité est considérée comme une pandémie responsable de plusieurs millions de morts dans le monde depuis de nombreuses années. Fin 2019 est apparue la maladie à Coronavirus 2019 (COVID-19) qui a provoqué la mort de plus d'un million de personnes en moins d'un an. De nombreuses études suggèrent que l'obésité pourrait être un paramètre clé dans l'apparition des formes graves de cette maladie émergente. En effet, le SARS-CoV2 infecte l'hôte en se fixant aux récepteurs ACE2 présents à la surface des cellules et entraîne une sécrétion excessive de cytokines pro-inflammatoires notamment l'IL-1, l'IL-6 et le TNF-α qui conduisent au développement d'un syndrome de détresse respiratoire aigu (SDRA). Il paraît essentiel d'élaborer des stratégies préventives efficaces pour protéger cette partie de la population du risque de développer une forme grave de COVID-19. L'alimentation cétogène, pauvre en sucres et riche en lipides, présente d'intéressantes propriétés, à la fois pour la lutte contre l'obésité mais également contre les infections sévères. Cet article fait le point sur les dernières avancées scientifiques qui permettent d'envisager l'alimentation cétogène comme une stratégie préventive visant à diminuer le développement de l'obésité et à renforcer le système immunitaire, deux actions clés dans la lutte contre l'infection au SARS-CoV2 et le développement de formes graves de COVID-19.


Subject(s)
COVID-19/prevention & control , Diet, Ketogenic , Inflammation/etiology , Obesity/prevention & control , Pandemics , SARS-CoV-2 , Adipocytes/metabolism , Animals , COVID-19/complications , COVID-19/immunology , COVID-19/physiopathology , Cytokine Release Syndrome/etiology , Diet, Ketogenic/adverse effects , Disease Susceptibility , Humans , Inflammation/physiopathology , Inflammation/prevention & control , Leptin/physiology , Obesity/complications , Obesity/diet therapy , Obesity/epidemiology , Respiratory Distress Syndrome/etiology
17.
Radiol Med ; 126(10): 1273-1281, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1305169

ABSTRACT

PURPOSE: The aim of the study was to prospectively evaluate the agreement between chest magnetic resonance imaging (MRI) and computed tomography (CT) and to assess the diagnostic performance of chest MRI relative to that of CT during the follow-up of patients recovered from coronavirus disease 2019. MATERIALS AND METHODS: Fifty-two patients underwent both follow-up chest CT and MRI scans, evaluated for ground-glass opacities (GGOs), consolidation, interlobular septal thickening, fibrosis, pleural indentation, vessel enlargement, bronchiolar ectasia, and changes compared to prior CT scans. DWI/ADC was evaluated for signal abnormalities suspicious for inflammation. Agreement between CT and MRI was assessed with Cohen's k and weighted k. Measures of diagnostic accuracy of MRI were calculated. RESULTS: The agreement between CT and MRI was almost perfect for consolidation (k = 1.00) and change from prior CT (k = 0.857); substantial for predominant pattern (k = 0.764) and interlobular septal thickening (k = 0.734); and poor for GGOs (k = 0.339), fibrosis (k = 0.224), pleural indentation (k = 0.231), and vessel enlargement (k = 0.339). Meanwhile, the sensitivity of MRI was high for GGOs (1.00), interlobular septal thickening (1.00), and consolidation (1.00) but poor for fibrotic changes (0.18), pleural indentation (0.23), and vessel enlargement (0.50) and the specificity was overall high. DWI was positive in 46.0% of cases. CONCLUSIONS: The agreement between MRI and CT was overall good. MRI was very sensitive for GGOs, consolidation and interlobular septal thickening and overall specific for most findings. DWI could be a reputable imaging biomarker of inflammatory activity.


Subject(s)
COVID-19/complications , Inflammation/diagnostic imaging , Inflammation/etiology , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Aged , COVID-19/physiopathology , Cohort Studies , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Inflammation/physiopathology , Lung/diagnostic imaging , Lung/physiopathology , Male , Middle Aged , Prospective Studies , Reproducibility of Results , SARS-CoV-2
18.
Nat Rev Nephrol ; 17(11): 751-764, 2021 11.
Article in English | MEDLINE | ID: covidwho-1297305

ABSTRACT

Although respiratory failure and hypoxaemia are the main manifestations of COVID-19, kidney involvement is also common. Available evidence supports a number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection. Histopathological findings have highlighted both similarities and differences between AKI in patients with COVID-19 and in those with AKI in non-COVID-related sepsis. Acute tubular injury is common, although it is often mild, despite markedly reduced kidney function. Systemic haemodynamic instability very likely contributes to tubular injury. Despite descriptions of COVID-19 as a cytokine storm syndrome, levels of circulating cytokines are often lower in patients with COVID-19 than in patients with acute respiratory distress syndrome with causes other than COVID-19. Tissue inflammation and local immune cell infiltration have been repeatedly observed and might have a critical role in kidney injury, as might endothelial injury and microvascular thrombi. Findings of high viral load in patients who have died with AKI suggest a contribution of viral invasion in the kidneys, although the issue of renal tropism remains controversial. An impaired type I interferon response has also been reported in patients with severe COVID-19. In light of these observations, the potential pathophysiological mechanisms of COVID-19-associated AKI may provide insights into therapeutic strategies.


Subject(s)
Acute Kidney Injury/physiopathology , Acute Kidney Injury/virology , COVID-19/physiopathology , Adaptive Immunity/physiology , Biopsy , Complement System Proteins , Drug-Related Side Effects and Adverse Reactions , Endothelium, Vascular/physiopathology , Extracorporeal Membrane Oxygenation , Hematuria/physiopathology , Humans , Immunity, Humoral/physiology , Immunity, Innate/physiology , Immunosenescence , Inflammation/physiopathology , Inflammation/virology , Interferon Type I/physiology , Kidney/pathology , Kidney/virology , Proteinuria/physiopathology , Severity of Illness Index , Viral Load
19.
Bioessays ; 43(9): e2000211, 2021 09.
Article in English | MEDLINE | ID: covidwho-1293142

ABSTRACT

We propose that hyper-inflammation (HYPi) is a ''runaway'' consequence of acute inflammation (ACUi) that arises more easily (and also abates less easily) in those who host a pre-existing chronic inflammation (CHRi), because (i) most factors involved in generating an ACUi to limit viral proliferation are already present when there is an underlying CHRi, and also because (ii) anti-inflammatory (AI) mechanisms for the abatement of ACUi (following containment of viral proliferation) are suppressed and desensitized where there is an underlying CHRi, with this causing the ACUi to spiral into a HYPi. Stress, pollution, diet, and gut microbiomes (alterable in weeks through dietary changes) have an intimate and bidirectional cause-effect relationship with CHRi. We propose that avoidance of CHRi-promoting foods and adoption of CHRi-suppressing foods could reduce susceptibility to HYPi, in Covid-19 and in other viral diseases, such as influenza, which are characterized by episodic and unpredictable HYPi.


Subject(s)
COVID-19 , Diet , Gastrointestinal Microbiome , Inflammation/physiopathology , COVID-19/diagnosis , COVID-19/physiopathology , Diet/adverse effects , Humans
20.
Int J Mol Sci ; 22(10)2021 May 17.
Article in English | MEDLINE | ID: covidwho-1238898

ABSTRACT

Inflammation is a key mechanism for the clearance of infective agents and other inflammatory triggers and is pivotal for the repairing processes of the affected tissues. Inflammation is a multistep process driven by a great number of mediators which regulate specific aspects of the inflammatory response, in agreement with a well-defined chronobiological program. A great number of inflammation-related diseases show a deeply altered immune chronobiology (e.g., COVID-19-related cytokines storm). This aspect highlights the need for a deeper understanding of the inflammatory phenomenon. It is fundamental to study inflammation as a multilevel phenomenon. Of particular interest is the low-grade chronic inflammation, which is an etiological factor of many chronic diseases. Nowadays, the therapeutic approach to low grade chronic inflammation is one of the great challenges of traditional pharmacology. Currently, no drugs specifically designed for the treatment of chronic inflammatory forms are available. Today, bioregulatory systems medicine (BrSM) and low dose medicine (LDM), two pharmacological paradigms grounded in systems medicine, potentially represent new tools for the treatment of inflammation-related diseases. Scientific research has assessed the effectiveness and safety of both these therapeutic approaches, in particular for the management of chronic inflammatory conditions and chronic immunological dysregulations.


Subject(s)
Anti-Inflammatory Agents/pharmacology , COVID-19/metabolism , Cytokine Release Syndrome/metabolism , Cytokines/metabolism , Inflammation/metabolism , Systems Analysis , Acute Disease , Anti-Inflammatory Agents/therapeutic use , COVID-19/immunology , COVID-19/physiopathology , Chronic Disease/drug therapy , Humans , Inflammation/drug therapy , Inflammation/immunology , Inflammation/physiopathology
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