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1.
Microbiol Spectr ; 10(1): e0127121, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1752773

ABSTRACT

The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global outbreak and prompted an enormous research effort. Still, the subcellular localization of the coronavirus in lungs of COVID-19 patients is not well understood. Here, the localization of the SARS-CoV-2 proteins is studied in postmortem lung material of COVID-19 patients and in SARS-CoV-2-infected Vero cells, processed identically. Correlative light and electron microscopy on semithick cryo-sections demonstrated induction of electron-lucent, lipid-filled compartments after SARS-CoV-2 infection in both lung and cell cultures. In lung tissue, the nonstructural protein 4 and the stable nucleocapsid N-protein were detected on these novel lipid-filled compartments. The induction of such lipid-filled compartments and the localization of the viral proteins in lung of patients with fatal COVID-19 may explain the extensive inflammatory response and provide a new hallmark for SARS-CoV-2 infection at the final, fatal stage of infection. IMPORTANCE Visualization of the subcellular localization of SARS-CoV-2 proteins in lung patient material of COVID-19 patients is important for the understanding of this new virus. We detected viral proteins in the context of the ultrastructure of infected cells and tissues and discovered that some viral proteins accumulate in novel, lipid-filled compartments. These structures are induced in Vero cells but, more importantly, also in lung of patients with COVID-19. We have characterized these lipid-filled compartments and determined that this is a novel, virus-induced structure. Immunogold labeling demonstrated that cellular markers, such as CD63 and lipid droplet marker PLIN-2, are absent. Colocalization of lipid-filled compartments with the stable N-protein and nonstructural protein 4 in lung of the last stages of COVID-19 indicates that these compartments play a key role in the devastating immune response that SARS-CoV-2 infections provoke.


Subject(s)
COVID-19/metabolism , Lipid Metabolism/physiology , Lipids/analysis , Lung/metabolism , Nucleocapsid/analysis , SARS-CoV-2 , Adolescent , Aged , Animals , COVID-19/pathology , Child, Preschool , Chlorocebus aethiops , Disease Outbreaks , Female , Fluorescent Antibody Technique , Humans , Immunohistochemistry , Lung/cytology , Lung/pathology , Lung/ultrastructure , Male , Microscopy, Immunoelectron , Middle Aged , Nucleocapsid/metabolism , Rabbits , SARS-CoV-2/ultrastructure , Vero Cells/virology
2.
Sci Rep ; 11(1): 21633, 2021 11 04.
Article in English | MEDLINE | ID: covidwho-1503836

ABSTRACT

Although the serum lipidome is markedly affected by COVID-19, two unresolved issues remain: how the severity of the disease affects the level and the composition of serum lipids and whether serum lipidome analysis may identify specific lipids impairment linked to the patients' outcome. Sera from 49 COVID-19 patients were analyzed by untargeted lipidomics. Patients were clustered according to: inflammation (C-reactive protein), hypoxia (Horowitz Index), coagulation state (D-dimer), kidney function (creatinine) and age. COVID-19 patients exhibited remarkable and distinctive dyslipidemia for each prognostic factor associated with reduced defense against oxidative stress. When patients were clustered by outcome (7 days), a peculiar lipidome signature was detected with an overall increase of 29 lipid species, including-among others-four ceramide and three sulfatide species, univocally related to this analysis. Considering the lipids that were affected by all the prognostic factors, we found one sphingomyelin related to inflammation and viral infection of the respiratory tract and two sphingomyelins, that are independently related to patients' age, and they appear as candidate biomarkers to monitor disease progression and severity. Although preliminary and needing validation, this report pioneers the translation of lipidome signatures to link the effects of five critical clinical prognostic factors with the patients' outcomes.


Subject(s)
COVID-19/metabolism , Lipids/blood , Serum/chemistry , Adult , Aged , Biomarkers/blood , COVID-19/blood , Dyslipidemias/metabolism , Female , Humans , Italy , Lipidomics/methods , Lipids/analysis , Male , Middle Aged , Oxidative Stress/physiology , Prognosis , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Sphingomyelins/blood
3.
Sci Rep ; 11(1): 5494, 2021 03 09.
Article in English | MEDLINE | ID: covidwho-1125236

ABSTRACT

It is important to pay attention to the indirect effects of the social distancing implemented to prevent the spread of coronavirus disease 2019 (COVID-19) pandemic on children and adolescent health. The aim of the present study was to explore impacts of a reduction in physical activity caused by COVID-19 outbreak in pediatric patients diagnosed with obesity. This study conducted between pre-school closing and school closing period and 90 patients aged between 6- and 18-year-old were included. Comparing the variables between pre-school closing period and school closing period in patients suffering from obesity revealed significant differences in variables related to metabolism such as body weight z-score, body mass index z-score, liver enzymes and lipid profile. We further evaluated the metabolic factors related to obesity. When comparing patients with or without nonalcoholic fatty liver disease (NAFLD), only hemoglobin A1c (HbA1c) was the only difference between the two time points (p < 0.05). We found that reduced physical activity due to school closing during COVID-19 pandemic exacerbated obesity among children and adolescents and negatively affects the HbA1C increase in NAFLD patients compared to non-NAFLD patients.


Subject(s)
COVID-19/pathology , Glucose Intolerance/diagnosis , Pediatric Obesity/diagnosis , Adolescent , Alanine Transaminase/analysis , Aspartate Aminotransferases/analysis , Body Mass Index , Body Weight , COVID-19/virology , Child , Exercise , Female , Glucose Intolerance/complications , Glycated Hemoglobin A/analysis , Humans , Lipids/analysis , Liver/enzymology , Male , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Pediatric Obesity/complications , Quarantine , SARS-CoV-2/isolation & purification
4.
Analyst ; 145(17): 5725-5732, 2020 Aug 24.
Article in English | MEDLINE | ID: covidwho-663353

ABSTRACT

The SARS-CoV-2 virus is known as the causal agent for the current COVID-19 global pandemic. The majority of COVID-19 patients develop acute respiratory distress syndrome (ARDS), while some experience a cytokine storm effect, which is considered as one of the leading causes of patient mortality. Lipids are known to be involved in the various stages of the lifecycle of a virus functioning as receptors or co-receptors that controls viral propagation inside the host cell. Therefore, lipid-related metabolomics aims to provide insight into the immune response of the novel coronavirus. Our study has focused on determination of the potential metabolomic biomarkers utilizing a Teslin® Substrate in paper spray mass spectrometry (PS-MS) for the development of a rapid detection test within 60 seconds of analysis time. In this study, results were correlated with PCR tests to reflect that the systemic responses of the cells were affected by the COVID-19 virus.


Subject(s)
Coronavirus Infections/pathology , Lipid Metabolism/physiology , Mass Spectrometry/methods , Pneumonia, Viral/pathology , Betacoronavirus/isolation & purification , Biomarkers/metabolism , COVID-19 , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Discriminant Analysis , Humans , Lipids/analysis , Nasopharynx/virology , Pandemics , Paper , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , SARS-CoV-2
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