Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 2.177
Filter
Add filters

Year range
1.
Medicine (Baltimore) ; 100(7): e24668, 2021 Feb 19.
Article in English | MEDLINE | ID: covidwho-1091183

ABSTRACT

ABSTRACT: We aimed to retrospectively analyze the clinical and computed tomography (CT) characteristics of young adults with Coronavirus Disease 2019 (COVID-19) pneumonia who were critically ill and to identify the features associated with non-survival.Thirty-eight COVID-19 patients (20-45 years old, 28 men) who had been admitted in the intensive care unit were included, including 18 non-survivors (group 1) and 20 survivors (group 2). Their clinical characteristics and initial and follow-up CT were compared between groups.In group 1, the days from illness onset to death were 21.1 ±â€Š10.3 days; 7 patients had underlying comorbidities. At admission, group 1 exhibited higher serum ferritin and interleukin-6 (IL-6) levels (1142.6 ±â€Š242.4 mg/L and 33.8 ±â€Š18.6 mmol/L) compared with group 2 (728.3 ±â€Š150.9 mg/L and 15.2 ±â€Š6.9 mmol/L, P < .01). Group 1 exhibited more rapidly progressive opacities and consolidation in follow-up CT (16.7 ±â€Š3.1 scores, 15.7 ±â€Š3.1 segments) than group 2 (11.4 ±â€Š4.0 scores, 10.3 ±â€Š4.6 segments, P < .01). The oxygenation index was lower (87.6 ±â€Š19.2 vs 99.1 ±â€Š20.4 mm Hg) and the mechanical ventilation duration was longer (14.7 ±â€Š6.9 vs 9.7 ±â€Š3.7 days) in group 1 compare with group 2 (P < .01).Compared with the survivors, the non-survivors showed higher serum ferritin and IL-6 levels, more rapidly progressive opacities in CT, lower oxygenation index, and longer mechanical ventilation durations. Special attention to ferritin/IL-6 levels and oxygenation index as well as early CT application and timely reexaminations are important to identify the individuals who may be at risk of becoming critically ill.


Subject(s)
/diagnosis , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Tomography, X-Ray Computed/methods , Adult , Critical Illness , Disease Progression , Female , Humans , Male , Pneumonia, Viral/virology , Retrospective Studies , Survival Analysis
2.
Crit Care ; 25(1): 53, 2021 02 08.
Article in English | MEDLINE | ID: covidwho-1069578

ABSTRACT

The current pandemic of COVID-19 caused thousands of deaths and healthcare professionals struggle to properly manage infected patients. This review summarizes information about SARS-CoV-2 receptor binding dynamics and intricacies, lung autopsy findings, immune response patterns, evidence-based explanations for the immune response, and COVID-19-associated hypercoagulability.


Subject(s)
/physiopathology , Carrier Proteins/physiology , Lung Diseases/physiopathology , Pneumonia, Viral/physiopathology , /pathogenicity , /immunology , Carrier Proteins/immunology , Humans , Lung Diseases/immunology , Pandemics , Pneumonia, Viral/immunology , /immunology
3.
J Exp Med ; 218(3)2021 03 01.
Article in English | MEDLINE | ID: covidwho-1044017

ABSTRACT

SARS-CoV-2, the causative agent of COVID-19, has been responsible for over 42 million infections and 1 million deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here, we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a Syrian hamster model of SARS-CoV-2 and in a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). Antibody combinations were effective for prevention and in therapy when administered early. However, in vitro antibody neutralization potency did not uniformly correlate with in vivo protection, and some hu-mAbs were more protective in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors contributes to optimal protection against SARS-CoV-2 MA. The data indicate that intact effector function can affect hu-mAb protective activity and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.


Subject(s)
Antibodies, Monoclonal, Murine-Derived , Antibodies, Neutralizing , Antibodies, Viral , Betacoronavirus/immunology , Coronavirus Infections , Pandemics , Pneumonia, Viral , Animals , Antibodies, Monoclonal, Murine-Derived/immunology , Antibodies, Monoclonal, Murine-Derived/pharmacology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/immunology , Antibodies, Viral/pharmacology , Cell Line , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Female , Humans , Mesocricetus , Mice , Mice, Inbred BALB C , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy
4.
Cell ; 182(4): 828-842.e16, 2020 08 20.
Article in English | MEDLINE | ID: covidwho-1027977

ABSTRACT

Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.


Subject(s)
Antibodies, Neutralizing/chemistry , Betacoronavirus/chemistry , Coronavirus Infections/immunology , Immunoglobulin Fab Fragments/chemistry , Immunoglobulin G/chemistry , Pneumonia, Viral/immunology , Spike Glycoprotein, Coronavirus/chemistry , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/immunology , Antibodies, Viral/isolation & purification , Betacoronavirus/immunology , Coronavirus Infections/blood , Coronavirus Infections/therapy , Cross Reactions , Cryoelectron Microscopy , Epitope Mapping , Epitopes , Humans , Immunization, Passive , Immunoglobulin Fab Fragments/blood , Immunoglobulin Fab Fragments/isolation & purification , Immunoglobulin Fab Fragments/ultrastructure , Immunoglobulin G/blood , Immunoglobulin G/isolation & purification , Immunoglobulin G/ultrastructure , Middle East Respiratory Syndrome Coronavirus/chemistry , Middle East Respiratory Syndrome Coronavirus/immunology , Models, Molecular , Pandemics , Pneumonia, Viral/blood , SARS Virus/chemistry , SARS Virus/immunology , Spike Glycoprotein, Coronavirus/immunology
7.
Int J Obes (Lond) ; 44(8): 1793-1799, 2020 08.
Article in English | MEDLINE | ID: covidwho-1023842

ABSTRACT

OBJECTIVE: Recent clinical trials have demonstrated that colchicine may have metabolic and cardiovascular and benefits in at-risk patients; however, the mechanisms through which colchicine may improve outcomes are still unclear. We sought to examine colchicine's effects on circulating inflammatory and metabolic molecules in adults with obesity and metabolic syndrome (MetS). METHODS: Blood samples were collected pre- and post-intervention during a double-blind randomized controlled trial in which 40 adults with obesity and MetS were randomized to colchicine 0.6 mg or placebo twice-daily for 3 months. Serum samples were analyzed for 1305 circulating factors using the SomaScan Platform. The Benjamini-Hochberg procedure was used to adjust the false discovery rate (FDR) for multiple testing. RESULTS: At baseline, age (48.0 ± 13.8 vs. 44.7 ± 10.3 years) and BMI (39.8 ± 6.4 vs. 41.8 ± 8.2 kg/m2) were not different between groups. After controlling for the FDR, 34 molecules were significantly changed by colchicine. Colchicine decreased concentrations of multiple inflammatory molecules, including C-reactive protein, interleukin 6, and resistin, in addition to vascular-related proteins (e.g., oxidized low-density lipoprotein receptor, phosphodiesterase 5A). Conversely, relative to placebo, colchicine significantly increased concentrations of eight molecules including secreted factors associated with metabolism and anti-thrombosis. CONCLUSIONS: In adults with obesity, colchicine significantly affected concentrations of proteins involved in the innate immune system, endothelial function and atherosclerosis, uncovering new mechanisms behind its cardiometabolic effects. Further research is warranted to investigate whether colchicine's IL-6 suppressive effects may be beneficial in COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Colchicine/therapeutic use , Coronavirus Infections/immunology , Metabolic Syndrome/complications , Metabolic Syndrome/immunology , Obesity/immunology , Pneumonia, Viral/immunology , Adult , Anti-Inflammatory Agents/pharmacology , Betacoronavirus/drug effects , C-Reactive Protein , Colchicine/pharmacology , Coronavirus Infections/drug therapy , Double-Blind Method , Female , Humans , Interleukin-6 , Male , Metabolic Syndrome/drug therapy , Middle Aged , Obesity/complications , Obesity/drug therapy , Pandemics , Pilot Projects , Pneumonia, Viral/drug therapy , Treatment Outcome , Young Adult
9.
Life Sci ; 253: 117723, 2020 Jul 15.
Article in English | MEDLINE | ID: covidwho-1023706

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/pathology , Myocardium/pathology , Pneumonia, Viral/pathology , Coronavirus Infections/immunology , Humans , Myocarditis/virology , Myocytes, Cardiac/pathology , Myocytes, Cardiac/virology , Pandemics , Pneumonia, Viral/immunology
13.
Nat Biotechnol ; 38(9): 1073-1078, 2020 09.
Article in English | MEDLINE | ID: covidwho-1023948

ABSTRACT

A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95-100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/genetics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Spike Glycoprotein, Coronavirus/genetics , Antibodies/immunology , Antibodies/pharmacology , Betacoronavirus/genetics , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Neutralization Tests , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Protein Interaction Domains and Motifs/genetics , Spike Glycoprotein, Coronavirus/chemistry
15.
Eur J Gastroenterol Hepatol ; 32(12): 1523-1526, 2020 12.
Article in English | MEDLINE | ID: covidwho-1020322

ABSTRACT

OBJECTIVES: Recent guidelines for celiac disease have allowed a biopsy-free approach in endomysial antibodies (EMAs) positive children with high antitransglutaminase (TGA-IgA) titer [>10 time upper limit of normal (ULN)]. Esophagogastroduodenoscopy is still necessary for diagnosis in children with lower title. Because elective pediatric endoscopy has been substantially shouted down during coronavirus disease (COVID-19) pandemic, many children remained undiagnosed - and therefore untreated - for a long time. We aimed to analyze the feasibility and accuracy of a biopsy-free approach in suspected celiac disease children with TGA-IgA values <10 ULN to facilitate the diagnostic process by avoiding endoscopy. METHODS: In this study cohort, we retrospectively analyzed all biopsy-confirmed diagnosis of celiac disease in our center (between 2014 and 2019). The positive predictive value (PPV) of TGA-IgA titers between 5 and 10 ULN and positive EMA in diagnosing celiac disease were determined. Mucosal atrophy and resolution of symptoms after gluten-free diet (GFD) were considered to confirm initial diagnosis. RESULTS: Of 430 celiac disease patients (F: 274; mean age 7.54 years) diagnosed by endoscopy, 84 (F: 46; mean age 8 years) with TGA-IgA between 5 and 10 ULN and positive EMA were identified. The PPV of TGA-IgA between 5 and 10 ULN and positive EMA was 0.93 (95% confidence interval 0.90-0.96). All these children had a symptom resolution and antibodies normalization after GFD. CONCLUSION: During the COVID-19 outbreak, a temporarily reduction of the TGA-IgA threshold for biopsy-sparing approach seems feasible in EMA positive children with TGA-IgA between 5 and 10 ULN.


Subject(s)
Autoantibodies/blood , Betacoronavirus , Celiac Disease/diagnosis , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Practice Guidelines as Topic , Transglutaminases/immunology , Autoantibodies/immunology , Biopsy , Celiac Disease/epidemiology , Celiac Disease/immunology , Child , Comorbidity , Coronavirus Infections/enzymology , Coronavirus Infections/immunology , Endoscopy, Digestive System , Female , Humans , Male , Pandemics , Pneumonia, Viral/enzymology , Pneumonia, Viral/immunology , Retrospective Studies , Transglutaminases/blood
SELECTION OF CITATIONS
SEARCH DETAIL