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1.
PLoS Comput Biol ; 17(3): e1008805, 2021 03.
Article in English | MEDLINE | ID: covidwho-1181166

ABSTRACT

Thrombosis is a recognized complication of Coronavirus disease of 2019 (COVID-19) and is often associated with poor prognosis. There is a well-recognized link between coagulation and inflammation, however, the extent of thrombotic events associated with COVID-19 warrants further investigation. Poly(A) Binding Protein Cytoplasmic 4 (PABPC4), Serine/Cysteine Proteinase Inhibitor Clade G Member 1 (SERPING1) and Vitamin K epOxide Reductase Complex subunit 1 (VKORC1), which are all proteins linked to coagulation, have been shown to interact with SARS proteins. We computationally examined the interaction of these with SARS-CoV-2 proteins and, in the case of VKORC1, we describe its binding to ORF7a in detail. We examined the occurrence of variants of each of these proteins across populations and interrogated their potential contribution to COVID-19 severity. Potential mechanisms, by which some of these variants may contribute to disease, are proposed. Some of these variants are prevalent in minority groups that are disproportionally affected by severe COVID-19. Therefore, we are proposing that further investigation around these variants may lead to better understanding of disease pathogenesis in minority groups and more informed therapeutic approaches.


Subject(s)
Blood Coagulation , Blood Proteins/genetics , Complement C1 Inhibitor Protein/genetics , Poly(A)-Binding Proteins/genetics , Vitamin K Epoxide Reductases/genetics , Anticoagulants/administration & dosage , Blood Proteins/metabolism , /virology , Complement C1 Inhibitor Protein/metabolism , Genome-Wide Association Study , Humans , Models, Molecular , Mutation , Poly(A)-Binding Proteins/metabolism , Protein Binding , Severity of Illness Index , Viral Proteins/metabolism , Vitamin K Epoxide Reductases/metabolism , Warfarin/administration & dosage
2.
Biosci Rep ; 41(3)2021 03 26.
Article in English | MEDLINE | ID: covidwho-1180288

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has induced an ongoing global health crisis. Here we utilized a combination of targeted amino acids (AAs) and clinical biochemical profiling to analyze the plasma of coronavirus disease 2019 (COVID-19) subjects at the hospitalization stage and 1-month post-infection convalescent stage, respectively, to investigate the systematic injury during COVID-19 disease progress. We found the virus-induced inflammatory status and reduced liver synthesis capacity in hospitalized patients, which manifested with increased branched-chain AAs (BCAAs), aromatic AAs (AAAs), one-carbon related metabolites, and decreased methionine. Most of these disturbances during infection recover except for the increased levels of medium-chain acylcarnitines (ACs) in the convalescent subjects, implying the existence of incomplete fatty acids oxidation during recovery periods. Our results suggested that the imbalance of the AA profiling in COVID-19 patients. The majority of disturbed AAs recovered in 1 month. The incomplete fatty acid oxidation products suggested it might take longer time for convalescent patients to get complete recovery.


Subject(s)
Amino Acids/metabolism , /virology , /physiology , Adult , Aged , Aged, 80 and over , Amino Acids/blood , Biomarkers , /epidemiology , Comorbidity , Female , Hospitalization , Host-Pathogen Interactions , Humans , Male , Metabolomics/methods , Middle Aged , Severity of Illness Index
4.
Clin Sci (Lond) ; 134(21): 2851-2871, 2020 11 13.
Article in English | MEDLINE | ID: covidwho-1177131

ABSTRACT

Angiotensin converting enzyme (ACE) is well-known for its role in blood pressure regulation via the renin-angiotensin aldosterone system (RAAS) but also functions in fertility, immunity, haematopoiesis and diseases such as obesity, fibrosis and Alzheimer's dementia. Like ACE, the human homologue ACE2 is also involved in blood pressure regulation and cleaves a range of substrates involved in different physiological processes. Importantly, it is the functional receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 responsible for the 2020, coronavirus infectious disease 2019 (COVID-19) pandemic. Understanding the interaction between SARS-CoV-2 and ACE2 is crucial for the design of therapies to combat this disease. This review provides a comparative analysis of methodologies and findings to describe how structural biology techniques like X-ray crystallography and cryo-electron microscopy have enabled remarkable discoveries into the structure-function relationship of ACE and ACE2. This, in turn, has enabled the development of ACE inhibitors for the treatment of cardiovascular disease and candidate therapies for the treatment of COVID-19. However, despite these advances the function of ACE homologues in non-human organisms is not yet fully understood. ACE homologues have been discovered in the tissues, body fluids and venom of species from diverse lineages and are known to have important functions in fertility, envenoming and insect-host defence mechanisms. We, therefore, further highlight the need for structural insight into insect and venom ACE homologues for the potential development of novel anti-venoms and insecticides.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/enzymology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/enzymology , Receptors, Virus/metabolism , Virus Internalization , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Host-Pathogen Interactions , Humans , Pandemics , Peptidyl-Dipeptidase A/chemistry , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Protein Conformation , Receptors, Virus/chemistry , Structure-Activity Relationship
5.
Eur J Endocrinol ; 184(5): 637-645, 2021 May.
Article in English | MEDLINE | ID: covidwho-1175452

ABSTRACT

Objective: Several recent observational studies have linked metabolic comorbidities to an increased risk from COVID-19. Here we investigated whether women with PCOS are at an increased risk of COVID-19 infection. Design: Population-based closed cohort study between 31 January 2020 and 22 July 2020 in the setting of a UK primary care database (The Health Improvement Network, THIN). Methods: The main outcome was the incidence of COVID-19 coded as suspected or confirmed by the primary care provider. We used Cox proportional hazards regression model with stepwise inclusion of explanatory variables (age, BMI, impaired glucose regulation, androgen excess, anovulation, vitamin D deficiency, hypertension, and cardiovascular disease) to provide unadjusted and adjusted hazard risks (HR) of COVID-19 infection among women with PCOS compared to women without PCOS. Results: We identified 21 292 women with a coded diagnosis of PCO/PCOS and randomly selected 78 310 aged and general practice matched control women. The crude COVID-19 incidence was 18.1 and 11.9 per 1000 person-years among women with and without PCOS, respectively. Age-adjusted Cox regression analysis suggested a 51% higher risk of COVID-19 among women with PCOS compared to women without PCOS (HR: 1.51 (95% CI: 1.27-1.80), P < 0.001). After adjusting for age and BMI, HR reduced to 1.36 (1.14-1.63)], P = 0.001. In the fully adjusted model, women with PCOS had a 28% increased risk of COVID-19 (aHR: 1.28 (1.05-1.56), P = 0.015). Conclusion: Women with PCOS are at an increased risk of COVID-19 infection and should be specifically encouraged to adhere to infection control measures during the COVID-19 pandemic. Significance statement: Women with polycystic ovary syndrome (PCOS) have an increased risk of cardio-metabolic disease, which have been identified as a risk factor for COVID-19. To investigate whether the increased metabolic risk in PCOS translates into an increased risk of COVID-19 infection, we carried out a population-based closed cohort study in the UK during its first wave of the SARS-CoV-2 pandemic (January to July 2020), including 21 292 women with PCOS and 78 310 controls matched for sex, age and general practice location. Results revealed a 52% increased risk of COVID-19 infection in women with PCOS, which remained increased at 28% above controls after adjustment for age, BMI, impaired glucose regulation and other explanatory variables.


Subject(s)
/epidemiology , Polycystic Ovary Syndrome/epidemiology , Adult , Age Factors , Body Mass Index , Cardiovascular Diseases/epidemiology , Diabetes Mellitus/epidemiology , Female , Humans , Hypertension/epidemiology , Middle Aged , Obesity/epidemiology , Polycystic Ovary Syndrome/metabolism , Prediabetic State/epidemiology , Proportional Hazards Models , Retrospective Studies , Risk Factors , Testosterone/metabolism , United Kingdom/epidemiology , Vitamin D Deficiency/epidemiology
6.
Biosci Rep ; 41(1)2021 01 29.
Article in English | MEDLINE | ID: covidwho-1174708

ABSTRACT

Millions of people infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been diagnosed with coronavirus infectious disease 2019 (COVID-19). The prevalence and severity of COVID-19 differ between sexes. To explain these differences, we analyzed clinical features and laboratory values in male and female COVID-19 patients. The present study included a cohort of 111 people, i.e. 36 COVID-19 patients, 54 sex- and age-matched common viral community-acquired pneumonia (CAP) patients, and 21 healthy controls. Monocyte counts, lymphocyte subset counts, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels in the peripheral blood were analyzed. Higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, monocyte counts, and CRP and ALT levels were found in male COVID-19 patients. Decreased lymphocyte subset counts and proportions were observed in COVID-19 patients, except for the CD3+ and CD8+ T cell proportions. The lower CD4+ T cell proportions and higher CD8+ T cell proportions were observed in male and severe COVID-19 patients and the differences were independent of estrogen level. The CD4+ T cell proportion was negatively associated with the CD8+ T cell proportion in male COVID-19 patients; this correlation was non-significant in females. Our work demonstrates differences between sexes in circulating monocyte counts and CD4+ T cell and CD8+ T cell proportions in COVID-19 patients, independent of estrogen levels, are associated with the clinical manifestations in COVID-19 patients with high specificity.


Subject(s)
/immunology , Immunity, Innate , Lymphocytes/virology , Monocytes/virology , Pneumonia, Viral/immunology , /pathogenicity , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , C-Reactive Protein/metabolism , CD4-CD8 Ratio , /virology , Case-Control Studies , Community-Acquired Infections , Estradiol/blood , Female , Humans , Leukocyte Count , Lymphocytes/immunology , Male , Middle Aged , Monocytes/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Severity of Illness Index , Sex Factors
7.
Biomolecules ; 10(8)2020 08 01.
Article in English | MEDLINE | ID: covidwho-1023242

ABSTRACT

Posttranslational modifications of cellular proteins by covalent conjugation of ubiquitin and ubiquitin-like polypeptides regulate numerous cellular processes that are captured by viruses to promote infection, replication, and spreading. The importance of these protein modifications for the viral life cycle is underscored by the discovery that many viruses encode deconjugases that reverse their functions. The structural and functional characterization of these viral enzymes and the identification of their viral and cellular substrates is providing valuable insights into the biology of viral infections and the host's antiviral defense. Given the growing body of evidence demonstrating their key contribution to pathogenesis, the viral deconjugases are now recognized as attractive targets for the design of novel antiviral therapeutics.


Subject(s)
Antiviral Agents/pharmacology , Enzymes/metabolism , Host-Pathogen Interactions/physiology , Ubiquitin/metabolism , Viral Proteins/metabolism , Virus Diseases/metabolism , Adenoviridae/enzymology , Coronavirus/enzymology , Enzymes/chemistry , Herpesviridae/enzymology , Humans , Protein Processing, Post-Translational , Viral Proteins/chemistry , Virus Diseases/drug therapy
8.
Methods Mol Biol ; 2203: 241-261, 2020.
Article in English | MEDLINE | ID: covidwho-729911

ABSTRACT

Coronavirus entry encompasses the initial steps of infection, from virion attachment to genome release. Advances in fluorescent labeling of viral and cellular components and confocal imaging enable broad spectrum studies on this process. Here, we describe methods for visualization of coronavirus entry into immortalized cell lines and 3D tissue culture models.


Subject(s)
Coronavirus/pathogenicity , Host-Pathogen Interactions/physiology , Microscopy, Confocal/methods , Cell Line , Coronavirus/isolation & purification , Culture Media/chemistry , Endocytosis , Humans , Nucleocapsid Proteins/metabolism , Triiodobenzoic Acids/chemistry , Virus Internalization
9.
Methods Mol Biol ; 2203: 231-238, 2020.
Article in English | MEDLINE | ID: covidwho-729910

ABSTRACT

Ribopuromycylation enables the visualization and quantitation of translation on a cellular level by immunofluorescence or in total using standard western blotting. This technique uses ribosome catalyzed puromycylation of nascent chains followed by immobilization on the ribosome by antibiotic chain elongation inhibitor emetine. Detection of puromycylated ribosome-bound nascent chains can then be achieved using a puromycin-specific antibody.


Subject(s)
Coronavirus/genetics , Puromycin/pharmacology , Coronavirus Infections , Fluorescent Antibody Technique , Host-Pathogen Interactions , Humans , Protein Biosynthesis , Ribosomes/drug effects , Ribosomes/metabolism
10.
Methods Mol Biol ; 2203: 187-204, 2020.
Article in English | MEDLINE | ID: covidwho-729907

ABSTRACT

Biotin-based proximity labeling circumvents major pitfalls of classical biochemical approaches to identify protein-protein interactions. It consists of enzyme-catalyzed biotin tags ubiquitously apposed on proteins located in close proximity of the labeling enzyme, followed by affinity purification and identification of biotinylated proteins by mass spectrometry. Here we outline the methods by which the molecular microenvironment of the coronavirus replicase/transcriptase complex (RTC), i.e., proteins located within a close perimeter of the RTC, can be determined by different proximity labeling approaches using BirAR118G (BioID), TurboID, and APEX2. These factors represent a molecular signature of coronavirus RTCs and likely contribute to the viral life cycle, thereby constituting attractive targets for the development of antiviral intervention strategies.


Subject(s)
Coronavirus/pathogenicity , Enzymes/genetics , Host-Pathogen Interactions/physiology , Proteomics/methods , Viral Proteins/metabolism , Animals , Ascorbate Peroxidases/genetics , Biotinylation , Carbon-Nitrogen Ligases/genetics , Cell Line , Coronavirus/genetics , Enzymes/metabolism , Escherichia coli Proteins/genetics , Fluorescent Antibody Technique , Microorganisms, Genetically-Modified , Repressor Proteins/genetics , Viral Proteins/chemistry , Viral Proteins/genetics
11.
Int J Mol Sci ; 22(1)2020 Dec 30.
Article in English | MEDLINE | ID: covidwho-1006614

ABSTRACT

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins' functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.


Subject(s)
Protein Processing, Post-Translational , RNA Virus Infections/enzymology , RNA Virus Infections/virology , RNA Viruses/metabolism , RNA Viruses/pathogenicity , Viral Proteins/metabolism , Acetylation , Chikungunya virus/metabolism , Coronavirus/metabolism , Coronavirus/pathogenicity , Cytopathogenic Effect, Viral , Glycosylation , HIV/metabolism , HIV/pathogenicity , Host Microbial Interactions , Humans , Phosphorylation , RNA Virus Infections/immunology , RNA Virus Infections/metabolism , RNA Viruses/immunology , Ubiquitination , Virus Replication/physiology , Zika Virus/metabolism , Zika Virus/pathogenicity
12.
J Biol Chem ; 295(51): 17781-17801, 2020 12 18.
Article in English | MEDLINE | ID: covidwho-985572

ABSTRACT

Knockout mouse models have been extensively used to study the antiviral activity of IFIT (interferon-induced protein with tetratricopeptide repeats). Human IFIT1 binds to cap0 (m7GpppN) RNA, which lacks methylation on the first and second cap-proximal nucleotides (cap1, m7GpppNm, and cap2, m7GpppNmNm, respectively). These modifications are signatures of "self" in higher eukaryotes, whereas unmodified cap0-RNA is recognized as foreign and, therefore, potentially harmful to the host cell. IFIT1 inhibits translation at the initiation stage by competing with the cap-binding initiation factor complex, eIF4F, restricting infection by certain viruses that possess "nonself" cap0-mRNAs. However, in mice and other rodents, the IFIT1 orthologue has been lost, and the closely related Ifit1b has been duplicated twice, yielding three paralogues: Ifit1, Ifit1b, and Ifit1c. Although murine Ifit1 is similar to human IFIT1 in its cap0-RNA-binding selectivity, the roles of Ifit1b and Ifit1c are unknown. Here, we found that Ifit1b preferentially binds to cap1-RNA, whereas binding is much weaker to cap0- and cap2-RNA. In murine cells, we show that Ifit1b can modulate host translation and restrict WT mouse coronavirus infection. We found that Ifit1c acts as a stimulatory cofactor for both Ifit1 and Ifit1b, promoting their translation inhibition. In this way, Ifit1c acts in an analogous fashion to human IFIT3, which is a cofactor to human IFIT1. This work clarifies similarities and differences between the human and murine IFIT families to facilitate better design and interpretation of mouse models of human infection and sheds light on the evolutionary plasticity of the IFIT family.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Coronavirus/growth & development , Coronavirus/genetics , Protein Biosynthesis , RNA Cap-Binding Proteins/metabolism , RNA Caps/metabolism , RNA-Binding Proteins/metabolism , Adaptor Proteins, Signal Transducing/deficiency , Adaptor Proteins, Signal Transducing/genetics , Animals , Coronavirus/metabolism , Disease Models, Animal , HEK293 Cells , Humans , Mice , Mice, Knockout , Models, Molecular , Mutation , Protein Binding , RAW 264.7 Cells , RNA-Binding Proteins/genetics
14.
Nat Commun ; 12(1): 2055, 2021 04 06.
Article in English | MEDLINE | ID: covidwho-1171493

ABSTRACT

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations.


Subject(s)
Antiviral Agents/pharmacology , /virology , Cross Reactions/immunology , Immunoassay/methods , T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Proliferation , Cytokines/metabolism , HEK293 Cells , Health Personnel , Humans , Immunoglobulin G/immunology , Immunologic Memory , Interferon-gamma/metabolism , Pandemics , Peptides/metabolism , /drug effects
15.
Emerg Microbes Infect ; 9(1): 727-732, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1169498

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with droplets and contact as the main means of transmission. Since the first case appeared in Wuhan, China, in December 2019, the outbreak has gradually spread nationwide. Up to now, according to official data released by the Chinese health commission, the number of newly diagnosed patients has been declining, and the epidemic is gradually being controlled. Although most patients have mild symptoms and good prognosis after infection, some patients developed severe and die from multiple organ complications. The pathogenesis of SARS-CoV-2 infection in humans remains unclear. Immune function is a strong defense against invasive pathogens and there is currently no specific antiviral drug against the virus. This article reviews the immunological changes of coronaviruses like SARS, MERS and other viral pneumonia similar to SARS-CoV-2. Combined with the published literature, the potential pathogenesis of COVID-19 is inferred, and the treatment recommendations for giving high-doses intravenous immunoglobulin and low-molecular-weight heparin anticoagulant therapy to severe type patients are proposed.


Subject(s)
Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Severe Acute Respiratory Syndrome/immunology , Animals , Antibodies, Viral/blood , Antibodies, Viral/immunology , Anticoagulants/therapeutic use , B-Lymphocytes/immunology , Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Coronavirus Infections/virology , Cytokines/immunology , Cytokines/metabolism , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Influenza A Virus, H1N1 Subtype , Influenza, Human/immunology , Mice , Middle East Respiratory Syndrome Coronavirus/immunology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , SARS Virus/immunology , T-Lymphocytes/immunology
16.
Int J Med Mushrooms ; 23(3): 1-14, 2021.
Article in English | MEDLINE | ID: covidwho-1170026

ABSTRACT

The most challenging threat facing the global community today is the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite global efforts to develop suitable treatments, very few specific antiviral agents have been suggested and the virus remains a serious global health risk. In vivo animal experiments have demonstrated that bioactive mycochemical constituents of Inonotus obliquus have immunomodulatory, antimicrobial, and antiviral properties. The present study investigates the antiviral potential of I. obliquus terpenoids against COVID-19 using a molecular docking study. The in silico study elucidates the ability of most of the terpenoid components to interact with the receptor-binding domain of SARS-CoV-2 spike glycoprotein with excellent affinity. Additionally, we found that both betulinic acid and inonotusane C could bind and stably interact with the spike protein near the host cell recognition site of angiotensin-converting enzyme 2.


Subject(s)
/drug therapy , Molecular Docking Simulation , Spike Glycoprotein, Coronavirus/drug effects , Terpenes/pharmacology , Inhibitory Concentration 50 , Molecular Structure , Spike Glycoprotein, Coronavirus/metabolism , Terpenes/chemistry , Terpenes/metabolism
17.
PLoS One ; 16(4): e0248357, 2021.
Article in English | MEDLINE | ID: covidwho-1169999

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a systemic disease that can rapidly progress into acute respiratory failure and death. Timely identification of these patients is crucial for a proper administration of health-care resources. OBJECTIVE: To develop a predictive score that estimates the risk of invasive mechanical ventilation (IMV) among patients with COVID-19. STUDY DESIGN: Retrospective cohort study of 401 COVID-19 patients diagnosed from March 12, to August 10, 2020. The score development cohort comprised 211 patients (52.62% of total sample) whereas the validation cohort included 190 patients (47.38% of total sample). We divided participants according to the need of invasive mechanical ventilation (IMV) and looked for potential predictive variables. RESULTS: We developed two predictive scores, one based on Interleukin-6 (IL-6) and the other one on the Neutrophil/Lymphocyte ratio (NLR), using the following variables: respiratory rate, SpO2/FiO2 ratio and lactic dehydrogenase (LDH). The area under the curve (AUC) in the development cohort was 0.877 (0.823-0.931) using the NLR based score and 0.891 (0.843-0.939) using the IL-6 based score. When compared with other similar scores developed for the prediction of adverse outcomes in COVID-19, the COVID-IRS scores proved to be superior in the prediction of IMV. CONCLUSION: The COVID-IRS scores accurately predict the need for mechanical ventilation in COVID-19 patients using readily available variables taken upon admission. More studies testing the applicability of COVID-IRS in other centers and populations, as well as its performance as a triage tool for COVID-19 patients are needed.


Subject(s)
/therapy , Hospitalization , Intubation , Respiration, Artificial , Adult , Aged , Biomarkers/metabolism , Female , Humans , Interleukin-6/metabolism , Male , Mexico , Middle Aged , Neutrophils/metabolism , Neutrophils/pathology , Respiratory Rate , Retrospective Studies , Risk Assessment , Triage
18.
Respir Res ; 22(1): 99, 2021 Apr 06.
Article in English | MEDLINE | ID: covidwho-1169963

ABSTRACT

BACKGROUND: COVID-19 pneumonia has been associated with severe acute hypoxia, sepsis-like states, thrombosis and chronic sequelae including persisting hypoxia and fibrosis. The molecular hypoxia response pathway has been associated with such pathologies and our recent observations on anti-hypoxic and anti-inflammatory effects of whole aqueous extract of Adhatoda Vasica (AV) prompted us to explore its effects on relevant preclinical mouse models. METHODS: In this study, we tested the effect of whole aqueous extract of AV, in murine models of bleomycin induced pulmonary fibrosis, Cecum Ligation and Puncture (CLP) induced sepsis, and siRNA induced hypoxia-thrombosis phenotype. The effect on lung of AV treated naïve mice was also studied at transcriptome level. We also determined if the extract may have any effect on SARS-CoV2 replication. RESULTS: Oral administration AV extract attenuates increased airway inflammation, levels of transforming growth factor-ß1 (TGF-ß1), IL-6, HIF-1α and improves the overall survival rates of mice in the models of pulmonary fibrosis and sepsis and rescues the siRNA induced inflammation and associated blood coagulation phenotypes in mice. We observed downregulation of hypoxia, inflammation, TGF-ß1, and angiogenesis genes and upregulation of adaptive immunity-related genes in the lung transcriptome. AV treatment also reduced the viral load in Vero cells infected with SARS-CoV2. CONCLUSION: Our results provide a scientific rationale for this ayurvedic herbal medicine in ameliorating the hypoxia-hyperinflammation features and highlights the repurposing potential of AV in COVID-19-like conditions.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Drug Repositioning , Hypoxia/drug therapy , Justicia , Lung/drug effects , Plant Extracts/pharmacology , Pneumonia/prevention & control , Pulmonary Fibrosis/drug therapy , Sepsis/drug therapy , Animals , Anti-Inflammatory Agents/isolation & purification , Bleomycin , /virology , Cecum/microbiology , Cecum/surgery , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Hypoxia/genetics , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor-Proline Dioxygenases/genetics , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Inflammation Mediators/metabolism , Justicia/chemistry , Ligation , Lung/metabolism , Lung/microbiology , Lung/pathology , Male , Mice, Inbred BALB C , Mice, Inbred C57BL , Plant Extracts/isolation & purification , Pneumonia/genetics , Pneumonia/metabolism , Pneumonia/microbiology , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/metabolism , RNA Interference , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Sepsis/genetics , Sepsis/metabolism , Sepsis/microbiology , Transcriptome
19.
Mol Med Rep ; 23(5)2021 May.
Article in English | MEDLINE | ID: covidwho-1167801

ABSTRACT

Although the COVID­19 epidemic has lasted for months, it has not yet been successfully controlled, and little is known about neonatal COVID­19. Therefore, literature search was conducted for references in PubMed, Science Direct, ProQuest, Web of Science and China National Knowledge Infrastructure for detailed case reports on neonatal COVID­19 published as of July 15, 2020, to facilitate the clinical treatment, epidemic prevention and control of neonatal COVID­19. Forty nonoverlapping case reports focusing mainly on the demographic characteristics, transmission modes, clinical features, treatments and prognosis of neonatal COVID­19, including 3 in Chinese and 37 in English, were available.


Subject(s)
/pathology , /physiology , Antibodies, Viral/analysis , Antiviral Agents/therapeutic use , Asymptomatic Diseases , /transmission , Humans , Infant, Newborn , Milk, Human/virology , RNA, Viral/metabolism , /immunology , Thorax/diagnostic imaging
20.
Molecules ; 26(7)2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1167670

ABSTRACT

Depression and anxiety disorders are widespread diseases, and they belong to the leading causes of disability and greatest burdens on healthcare systems worldwide. It is expected that the numbers will dramatically rise during the COVID-19 pandemic. Established medications are not sufficient to adequately treat depression and are not available for everyone. Plants from traditional medicine may be promising alternatives to treat depressive symptoms. The model organism Chaenorhabditis elegans was used to assess the stress reducing effects of methanol/dichlormethane extracts from plants used in traditional medicine. After initial screening for antioxidant activity, nine extracts were selected for in vivo testing in oxidative stress, heat stress, and osmotic stress assays. Additionally, anti-aging properties were evaluated in lifespan assay. The extracts from Acanthopanax senticosus, Campsis grandiflora, Centella asiatica, Corydalis yanhusuo, Dan Zhi, Houttuynia cordata, Psoralea corylifolia, Valeriana officinalis, and Withaniasomnifera showed antioxidant activity of more than 15 Trolox equivalents per mg extract. The extracts significantly lowered ROS in mutants, increased resistance to heat stress and osmotic stress, and the extended lifespan of the nematodes. The plant extracts tested showed promising results in increasing stress resistance in the nematode model. Further analyses are needed, in order to unravel underlying mechanisms and transfer results to humans.


Subject(s)
Antidepressive Agents/pharmacology , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/physiology , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Aging/drug effects , Aging/physiology , Animals , Antioxidants/pharmacology , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Gene Knockout Techniques , Heat-Shock Response/drug effects , Longevity/drug effects , Longevity/genetics , Longevity/physiology , Mutation , Osmotic Pressure/drug effects , Oxidative Stress/drug effects , Plant Extracts/chemistry , Reactive Oxygen Species/metabolism
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