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1.
Iran J Immunol ; 18(1): 47-53, 2021 03.
Статья в английский | MEDLINE | ID: covidwho-2091347

Реферат

BACKGROUND: Incidence and severity of SARS-CoV2 infection are significantly lower in children and teenagers proposing that certain vaccines, routinely administered to neonates and children may provide cross-protection against this emerging infection. OBJECTIVE: To assess the cross-protection induced by prior measles, mumps and rubella (MMR) vaccinations against COVID-19. METHODS: The antibody responses to MMR and tetanus vaccines were determined in 53 patients affected with SARS-CoV2 infection and 52 age-matched healthy subjects. Serum levels of antibodies specific for NP and RBD of SARS-CoV2 were also determined in both groups of subjects with ELISA. RESULTS: Our results revealed significant differences in anti-NP (P<0.0001) and anti-RBD (P<0.0001) IgG levels between patients and healthy controls. While the levels of rubella- and mumps specific IgG were not different in the two groups of subjects, measles-specific IgG was significantly higher in patients (P<0.01). The serum titer of anti-tetanus antibody, however, was significantly lower in patients compared to healthy individuals (P<0.01). CONCLUSION: Our findings suggest that measles vaccination triggers those B cells cross-reactive with SARS-CoV2 antigens leading to the production of increased levels of measles-specific antibody.


Тема - темы
Antibodies, Viral/blood , Antigens, Viral/immunology , COVID-19/immunology , Immunization , Immunoglobulin G/blood , Measles-Mumps-Rubella Vaccine/therapeutic use , SARS-CoV-2/immunology , Age Factors , Aged , B-Lymphocytes/immunology , B-Lymphocytes/virology , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/virology , Case-Control Studies , Cross Protection , Cross Reactions , Female , Host-Pathogen Interactions , Humans , Male , Measles-Mumps-Rubella Vaccine/immunology , Middle Aged , Tetanus Toxoid/immunology , Tetanus Toxoid/therapeutic use
3.
Iran J Immunol ; 18(1): 82-92, 2021 03.
Статья в английский | MEDLINE | ID: covidwho-2067500

Реферат

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly transmits in general population, mainly between health-care workers (HCWs) who are in close contact with patients. OBJECTIVE: To study the seropositivity of HCWs as a high-risk group compared to general population. METHODS: 72 samples were obtained from HCWs working in Masih Daneshvari hospital as one of the main COVID-19 admission centers in Tehran, during April 4 to 6, 2020. Also we collected 2021 blood samples from general population. The SARS-CoV-2 specific IgM, and IgG antibodies in the collected serum specimens were measured by commercial ELISA kits. RESULTS: Based on the clinical manifestations, 25.0%, 47.2%, and 27.8% of HCWs were categorized as symptomatic with typical symptoms, symptomatic with atypical symptoms, and asymptomatic, respectively. Symptomatic individuals with typical and atypical symptoms were 63.2% and 36.8% positive in RT-PCR test, respectively. Anti-SARS-CoV-2 IgM and IgG antibodies were detected in 15.3% and 27.8% of HCWs samples, respectively. Antibody testing in the general population indicated that SARS-CoV-2 specific IgM and IgG were found in (162/2021) 8%, and (290/2021) 14.4%, respectively. The frequency of positive cases of IgM and IgG were significantly increased in HCWs compared to general population (p= 0.028 for IgM and p= 0.002 for IgG). CONCLUSION: The frequency of SARS-CoV-2 specific antibodies in HCWs was higher than general population indicating a higher viral transmission via close exposure with COVID-19 patients.


Тема - темы
Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19/diagnosis , Health Personnel , Occupational Health , SARS-CoV-2/immunology , Adult , Aged , Biomarkers/blood , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , Cross-Sectional Studies , Female , Host-Pathogen Interactions , Humans , Infectious Disease Transmission, Patient-to-Professional , Iran/epidemiology , Male , Middle Aged , Occupational Exposure , Predictive Value of Tests , Risk Factors , Seroepidemiologic Studies , Time Factors , Young Adult
4.
Mol Med ; 28(1): 122, 2022 10 10.
Статья в английский | MEDLINE | ID: covidwho-2064734

Реферат

BACKGROUND: Long-COVID is characterized by prolonged, diffuse symptoms months after acute COVID-19. Accurate diagnosis and targeted therapies for Long-COVID are lacking. We investigated vascular transformation biomarkers in Long-COVID patients. METHODS: A case-control study utilizing Long-COVID patients, one to six months (median 98.5 days) post-infection, with multiplex immunoassay measurement of sixteen blood biomarkers of vascular transformation, including ANG-1, P-SEL, MMP-1, VE-Cad, Syn-1, Endoglin, PECAM-1, VEGF-A, ICAM-1, VLA-4, E-SEL, thrombomodulin, VEGF-R2, VEGF-R3, VCAM-1 and VEGF-D. RESULTS: Fourteen vasculature transformation blood biomarkers were significantly elevated in Long-COVID outpatients, versus acutely ill COVID-19 inpatients and healthy controls subjects (P < 0.05). A unique two biomarker profile consisting of ANG-1/P-SEL was developed with machine learning, providing a classification accuracy for Long-COVID status of 96%. Individually, ANG-1 and P-SEL had excellent sensitivity and specificity for Long-COVID status (AUC = 1.00, P < 0.0001; validated in a secondary cohort). Specific to Long-COVID, ANG-1 levels were associated with female sex and a lack of disease interventions at follow-up (P < 0.05). CONCLUSIONS: Long-COVID patients suffer prolonged, diffuse symptoms and poorer health. Vascular transformation blood biomarkers were significantly elevated in Long-COVID, with angiogenesis markers (ANG-1/P-SEL) providing classification accuracy of 96%. Vascular transformation blood biomarkers hold potential for diagnostics, and modulators of angiogenesis may have therapeutic efficacy.


Тема - темы
Biomarkers , COVID-19 , Biomarkers/blood , COVID-19/complications , Case-Control Studies , Endoglin , Female , Humans , Integrin alpha4beta1 , Intercellular Adhesion Molecule-1 , Matrix Metalloproteinase 1 , Neovascularization, Pathologic , Platelet Endothelial Cell Adhesion Molecule-1 , Thrombomodulin , Vascular Cell Adhesion Molecule-1 , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor D
5.
Nucleic Acids Res ; 50(D1): D777-D784, 2022 01 07.
Статья в английский | MEDLINE | ID: covidwho-2062936

Реферат

GMrepo (data repository for Gut Microbiota) is a database of curated and consistently annotated human gut metagenomes. Its main purposes are to increase the reusability and accessibility of human gut metagenomic data, and enable cross-project and phenotype comparisons. To achieve these goals, we performed manual curation on the meta-data and organized the datasets in a phenotype-centric manner. GMrepo v2 contains 353 projects and 71,642 runs/samples, which are significantly increased from the previous version. Among these runs/samples, 45,111 and 26,531 were obtained by 16S rRNA amplicon and whole-genome metagenomics sequencing, respectively. We also increased the number of phenotypes from 92 to 133. In addition, we introduced disease-marker identification and cross-project/phenotype comparison. We first identified disease markers between two phenotypes (e.g. health versus diseases) on a per-project basis for selected projects. We then compared the identified markers for each phenotype pair across datasets to facilitate the identification of consistent microbial markers across datasets. Finally, we provided a marker-centric view to allow users to check if a marker has different trends in different diseases. So far, GMrepo includes 592 marker taxa (350 species and 242 genera) for 47 phenotype pairs, identified from 83 selected projects. GMrepo v2 is freely available at: https://gmrepo.humangut.info.


Тема - темы
Databases, Genetic , Intestinal Neoplasms/microbiology , Metagenome , Microbiota , Biomarkers/blood , Datasets as Topic , Gastrointestinal Microbiome/genetics , High-Throughput Nucleotide Sequencing , Humans , Internet , Intestinal Neoplasms/blood , Intestinal Neoplasms/genetics , Intestinal Neoplasms/pathology , Molecular Sequence Annotation , Phenotype , RNA, Ribosomal, 16S , Software
6.
Niger J Clin Pract ; 25(9): 1418-1423, 2022 Sep.
Статья в английский | MEDLINE | ID: covidwho-2055768

Реферат

Background: In coronavirus disease 2019 (COVID-19) caused by SARSCoV2 viruses, coagulation abnormalities are strongly correlated between disease severity and mortality risk. Aims: The aim was to search for new indices to determine mortality risk. Fibrinogen times D-dimer to albumin times platelet ratio calculated with the formula (FDAPR index: ((Fibrinogen × D-dimer)/(Albumin × Platelet)) investigated as a mortality marker in COVID-19 patients. The hospitalization data of 1124 patients were analyzed from the electronic archive system. Hemogram, coagulation, and inflammatory markers were investigated in the study group. Materials and Methods: All statistical analyses like the student t-test, Mann-Whitney U, Kaplan-Meier, and Cox hazard ratio, were performed with the SPSS 22.0 program. Results: Prothrombin time was prolonged significantly in patients (P < 0.05) compared to healthy subjects (n = 30). D-dimer and fibrinogen were high, and albumin and platelet counts were low in COVID-19 patients (all, P < 0.001). When the data of 224 non-survivors and 900 survived patients were compared, D-dimer and fibrinogen were higher, and albumin and platelet lower (all, P < 0.001) compared to mild and severe patients. At the cut-off value of 0.49, the FDAPR index was performed with 89.1% sensitivity and 88.6% specificity. FDAPR index had the highest mortality predictive power (P < 0.01; HR = 5.366; 95% CI; 1.729-16.654). Conclusions: This study revealed that the FDAPR index could be used as a mortality marker of COVID-19 disease.


Тема - темы
COVID-19 , Albumins , Biomarkers/blood , COVID-19/blood , COVID-19/mortality , Fibrin Fibrinogen Degradation Products , Fibrinogen , Humans , Retrospective Studies , SARS-CoV-2
7.
J Neurol Neurosurg Psychiatry ; 93(12): 1343-1348, 2022 Dec.
Статья в английский | MEDLINE | ID: covidwho-2038335

Реферат

BACKGROUND: To assess whether SARS-CoV-2 infection may affect the central nervous system, specifically neurons and glia cells, even without clinical neurological involvement. METHODS: In this single centre prospective study, serum levels of neurofilament light chain (sNfL) and glial fibrillar acidic protein (sGFAp) were assessed using SimoaTM assay Neurology 2-Plex B Assay Kit, in 148 hospitalised patients with COVID-19 without clinical neurological manifestations and compared them to 53 patients with interstitial pulmonary fibrosis (IPF) and 108 healthy controls (HCs). RESULTS: Age and sex-corrected sNfL levels were higher in patients with COVID-19 (median log10-sNfL 1.41; IQR 1.04-1.83) than patients with IPF (median log10-sNfL 1.18; IQR 0.98-1.38; p<0.001) and HCs (median log10-sNfL 0.89; IQR 0.72-1.14; p<0.001). Likewise, age and sex-corrected sGFAP levels were higher in patients with COVID-19 (median log10-sGFAP 2.26; IQR 2.02-2.53) in comparison with patients with IPF (median log10-sGFAP 2.15; IQR 1.94-2.30; p<0.001) and HCs (median log10-sGFAP 1.87; IQR 0.64-2.09; p<0.001). No significant difference was found between patients with HCs and IPF (p=0.388 for sNfL and p=0.251 for sGFAp). In patients with COVID-19, a prognostic model with mortality as dependent variable (26/148 patients died during hospitalisation) and sNfl, sGFAp and age as independent variables, showed an area under curve of 0.72 (95% CI 0.59 to 0.84; negative predictive value (NPV) (%):80,positive predictive value (PPV)(%): 84; p=0.0008). CONCLUSION: The results of our study suggest that neuronal and glial degeneration can occur in patients with COVID-19 regardless of overt clinical neurological manifestations. With age, levels of sNfl and GFAp can predict in-hospital COVID-19-associated mortality and might be useful to assess COVID-19 patient prognostic profile.


Тема - темы
Brain , COVID-19 , Neuroglia , Neurons , Humans , Biomarkers/blood , Brain/pathology , Brain/virology , COVID-19/mortality , COVID-19/pathology , Neurofilament Proteins/blood , Neuroglia/pathology , Neuroglia/virology , Neurons/pathology , Neurons/virology , Prospective Studies , SARS-CoV-2 , Male , Female , Prognosis
8.
Front Immunol ; 13: 946522, 2022.
Статья в английский | MEDLINE | ID: covidwho-2022727

Реферат

Numerous publications have underlined the link between complement C5a and the clinical course of COVID-19. We previously reported that levels of C5a remain high in the group of severely ill patients up to 90 days after hospital discharge. We have now evaluated which complement pathway fuels the elevated levels of C5a during hospitalization and follow-up. The alternative pathway (AP) activation marker C3bBbP and the soluble fraction of C4d, a footprint of the classical/lectin (CP/LP) pathway, were assessed by immunoenzymatic assay in a total of 188 serial samples from 49 patients infected with SARS-CoV-2. Unlike C5a, neither C3bBbP nor C4d readouts rose proportionally to the severity of the disease. Detailed correlation analyses in hospitalization and follow-up samples collected from patients of different disease severity showed significant positive correlations of AP and CP/LP markers with C5a in certain groups, except for the follow-up samples of the patients who suffered from highly severe COVID-19 and presented the highest C5a readouts. In conclusion, there is not a clear link between persistently high levels of C5a after hospital discharge and markers of upstream complement activation, suggesting the existence of a non-canonical source of C5a in patients with a severe course of COVID-19.


Тема - темы
COVID-19 , Complement Activation , Complement C3b , Complement C4b , Complement C5a , Complement Factor B , Peptide Fragments , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , Complement Activation/immunology , Complement C3b/immunology , Complement C4b/immunology , Complement C5a/analysis , Complement C5a/immunology , Complement Factor B/immunology , Complement System Proteins/immunology , Humans , Peptide Fragments/immunology , SARS-CoV-2
9.
Int J Mol Sci ; 23(16)2022 Aug 15.
Статья в английский | MEDLINE | ID: covidwho-1987836

Реферат

The persistence of long-term coronavirus-induced disease 2019 (COVID-19) sequelae demands better insights into its natural history. Therefore, it is crucial to discover the biomarkers of disease outcome to improve clinical practice. In this study, 160 COVID-19 patients were enrolled, of whom 80 had a "non-severe" and 80 had a "severe" outcome. Sera were analyzed by proximity extension assay (PEA) to assess 274 unique proteins associated with inflammation, cardiometabolic, and neurologic diseases. The main clinical and hematochemical data associated with disease outcome were grouped with serological data to form a dataset for the supervised machine learning techniques. We identified nine proteins (i.e., CD200R1, MCP1, MCP3, IL6, LTBP2, MATN3, TRANCE, α2-MRAP, and KIT) that contributed to the correct classification of COVID-19 disease severity when combined with relative neutrophil and lymphocyte counts. By analyzing PEA, clinical and hematochemical data with statistical methods that were able to handle many variables in the presence of a relatively small sample size, we identified nine potential serum biomarkers of a "severe" outcome. Most of these were confirmed by literature data. Importantly, we found three biomarkers associated with central nervous system pathologies and protective factors, which were downregulated in the most severe cases.


Тема - темы
COVID-19 , Proteomics , Biomarkers/blood , COVID-19/diagnosis , Humans , Lymphocyte Count , Machine Learning
10.
BMJ ; 375: n2400, 2021 10 14.
Статья в английский | MEDLINE | ID: covidwho-1978540

Реферат

OBJECTIVE: To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards. DESIGN: Randomised controlled, adaptive, open label clinical trial. SETTING: 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US. PARTICIPANTS: 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237). INTERVENTIONS: Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death. MAIN OUTCOME MEASURES: The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated. RESULTS: The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m2. At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69). CONCLUSIONS: In moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04362085.


Тема - темы
Anticoagulants/therapeutic use , COVID-19/mortality , COVID-19/therapy , Heparin/therapeutic use , Hospitalization/statistics & numerical data , Respiration, Artificial , Biomarkers/blood , Female , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , SARS-CoV-2 , Severity of Illness Index
11.
Biochemistry (Mosc) ; 87(3): 207-214, 2022 Mar.
Статья в английский | MEDLINE | ID: covidwho-1973803

Реферат

In this study, we aimed to determine whether the progranulin level in serum predicts the course and severity of the disease in COVID-19 (+) patients and whether it can be used as a biomarker in these patients. Therefore, we sampled 61 people infected with COVID-19, and the cases were divided into the following groups: asymptomatic, noncomplicated, moderate, and severe. Concentrations of progranulin, TNF-α, IL-6 from in serum obtained from all participants were measured using commercially available ELISA kits, as well as WBC, PLT, NE, LY, ALT, AST, Hb, PCT, and CRP were examined with clinical analyzer. All measurements obtained for the patient samples were compared with those of 20 healthy individuals. The serum progranulin concentration was statistically higher in the COVID-19 (+) patient group than in the control group of healthy individuals [112.6 ± 54.8, 0.0 (0.0-54.2 pg/ml, respectively p = 0.000)]. ROC analysis was performed to evaluate the progranulin potential as a biomarker for COVID-19 (+) patients. A larger AUC (0.931 ± 0.08) value and a more significant p-value for progranulin than for CRP (p = 0.000) was detected. As a result, we believe that progranulin reaches high levels in the COVID-19 disease and may be a determinant in diagnosis and prognosis, and may be a better biomarker than CRP.


Тема - темы
COVID-19 , Progranulins , Biomarkers/blood , C-Reactive Protein , COVID-19/diagnosis , Humans , Pilot Projects , Prognosis , Progranulins/blood , ROC Curve
12.
PLoS Negl Trop Dis ; 14(6): e0008407, 2020 06.
Статья в английский | MEDLINE | ID: covidwho-1962982

Реферат

Confronted with the challenge of understanding population-level processes, disease ecologists and epidemiologists often simplify quantitative data into distinct physiological states (e.g. susceptible, exposed, infected, recovered). However, data defining these states often fall along a spectrum rather than into clear categories. Hence, the host-pathogen relationship is more accurately defined using quantitative data, often integrating multiple diagnostic measures, just as clinicians do to assess their patients. We use quantitative data on a major neglected tropical disease (Leptospira interrogans) in California sea lions (Zalophus californianus) to improve individual-level and population-level understanding of this Leptospira reservoir system. We create a "host-pathogen space" by mapping multiple biomarkers of infection (e.g. serum antibodies, pathogen DNA) and disease state (e.g. serum chemistry values) from 13 longitudinally sampled, severely ill individuals to characterize changes in these values through time. Data from these individuals describe a clear, unidirectional trajectory of disease and recovery within this host-pathogen space. Remarkably, this trajectory also captures the broad patterns in larger cross-sectional datasets of 1456 wild sea lions in all states of health but sampled only once. Our framework enables us to determine an individual's location in their time-course since initial infection, and to visualize the full range of clinical states and antibody responses induced by pathogen exposure. We identify predictive relationships between biomarkers and outcomes such as survival and pathogen shedding, and use these to impute values for missing data, thus increasing the size of the useable dataset. Mapping the host-pathogen space using quantitative biomarker data enables more nuanced understanding of an individual's time course of infection, duration of immunity, and probability of being infectious. Such maps also make efficient use of limited data for rare or poorly understood diseases, by providing a means to rapidly assess the range and extent of potential clinical and immunological profiles. These approaches yield benefits for clinicians needing to triage patients, prevent transmission, and assess immunity, and for disease ecologists or epidemiologists working to develop appropriate risk management strategies to reduce transmission risk on a population scale (e.g. model parameterization using more accurate estimates of duration of immunity and infectiousness) and to assess health impacts on a population scale.


Тема - темы
Biomarkers/blood , Host-Pathogen Interactions/physiology , Leptospira/pathogenicity , Leptospirosis/diagnosis , Leptospirosis/veterinary , Sea Lions/microbiology , Animal Diseases/diagnosis , Animal Diseases/immunology , Animal Diseases/microbiology , Animals , Antibodies, Bacterial/blood , Bacterial Shedding , California , Cross-Sectional Studies , Host-Pathogen Interactions/immunology , Immunity , Kinetics , Leptospira interrogans , Leptospirosis/immunology , Survival Rate
13.
Int J Obes (Lond) ; 46(10): 1801-1807, 2022 10.
Статья в английский | MEDLINE | ID: covidwho-1937412

Реферат

BACKGROUND/OBJECTIVES: Patients affected by obesity and Coronavirus disease 2019, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appear to have a higher risk for intensive care (ICU) admission. A state of low-grade chronic inflammation in obesity has been suggested as one of the underlying mechanisms. We investigated whether obesity is associated with differences in new inflammatory biomarkers mid-regional proadrenomedullin (MR-proADM), C-terminal proendothelin-1 (CT-proET-1), and clinical outcomes in critically ill patients with SARS-CoV-2 pneumonia. SUBJECTS/METHODS: A total of 105 critically ill patients with SARS-CoV-2 pneumonia were divided in patients with obesity (body mass index (BMI) ≥ 30 kg/m2, n = 42) and patients without obesity (BMI < 30 kg/m2, n = 63) and studied in a retrospective observational cohort study. MR-proADM, CT-proET-1 concentrations, and conventional markers of white blood count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) were collected during the first 7 days. RESULTS: BMI was 33.5 (32-36.1) and 26.2 (24.7-27.8) kg/m2 in the group with and without obesity. There were no significant differences in concentrations MR-proADM, CT-proET-1, WBC, CRP, and PCT at baseline and the next 6 days between patients with and without obesity. Only MR-proADM changed significantly over time (p = 0.039). Also, BMI did not correlate with inflammatory biomarkers (MR-proADM rho = 0.150, p = 0.125, CT-proET-1 rho = 0.179, p = 0.067, WBC rho = -0.044, p = 0.654, CRP rho = 0.057, p = 0.564, PCT rho = 0.022, p = 0.842). Finally, no significant differences in time on a ventilator, ICU length of stay, and 28-day mortality between patients with or without obesity were observed. CONCLUSIONS: In critically ill patients with confirmed SARS-CoV-2 pneumonia, obesity was not associated with differences in MR-proADM, and CT-proET-1, or impaired outcome. TRIAL REGISTRATION: Netherlands Trial Register, NL8460.


Тема - темы
Adrenomedullin , COVID-19 , Endothelin-1 , Obesity , Peptide Fragments , Protein Precursors , SARS-CoV-2 , Adrenomedullin/blood , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/complications , COVID-19/diagnosis , Critical Care , Critical Illness , Disease Progression , Endothelin-1/blood , Humans , Obesity/complications , Patient Admission , Peptide Fragments/blood , Procalcitonin/blood , Prognosis , Protein Precursors/blood , Retrospective Studies
14.
Hosp Pediatr ; 12(7): e261-e265, 2022 07 01.
Статья в английский | MEDLINE | ID: covidwho-1923745

Реферат

BACKGROUND AND OBJECTIVES: N-terminal of probrain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels are often elevated in multisystem inflammatory syndrome in children (MIS-C) secondary to inflammation, myocardial dysfunction, or increased wall tension. Intravenous immunoglobulin (IVIG), accepted treatment of MIS-C, may transiently increase myocardial tension and contribute to an increase in NT-proBNP. We sought to study the association between pre- and post-IVIG levels of NT-proBNP and CRP and their clinical significance. METHODS: This single-center, retrospective, cohort study included consecutive children, aged ≤21 years, with diagnosis of MIS-C who received IVIG from April 2020 to October 2021. Data collection included clinical characteristics, laboratory tests, management, and outcomes. Study cohort consisted of patients who received IVIG and had NT-proBNP levels available pre- and post-IVIG. RESULTS: Among 35 patients with MIS-C, 30 met inclusion criteria. Twenty-four, 80%, showed elevation in NT-proBNP post-IVIG. The median NT-proBNP level pre-IVIG was 1921 pg/mL (interquartile range 548-3956), significantly lower than the post-IVIG median of 3756 pg/mL (interquartile range 1342-7634)) (P = .0010). The median pre-IVIG CRP level was significantly higher than the post-IVIG level (12 mg/dL vs 8 mg/dL, P = .0006). All but 1 recovered before discharge, and none had signs of worsening cardiac function post-IVIG. In those who recovered, NT-proBNP had normalized by discharge or 1-week follow-up. CONCLUSIONS: Our study shows that NT-proBNP levels often transiently increase immediately after IVIG therapy without signs of worsening myocardial function. These values should be interpreted in the context of CRP levels and clinical recovery.


Тема - темы
COVID-19 , Immunoglobulins, Intravenous , Natriuretic Peptide, Brain , Systemic Inflammatory Response Syndrome , Biomarkers/blood , COVID-19/blood , COVID-19/drug therapy , Child , Humans , Immunoglobulins, Intravenous/therapeutic use , Natriuretic Peptide, Brain/blood , Peptide Fragments , Retrospective Studies , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/drug therapy
15.
PLoS One ; 17(2): e0262487, 2022.
Статья в английский | MEDLINE | ID: covidwho-1910491

Реферат

BACKGROUND: Coronavirus disease (COVID-19) has a severe impact on all aspects of patient care. Among the numerous biomarkers of potential validity for diagnostic and clinical management of COVID-19 are biomarkers at the interface of iron metabolism and inflammation. METHODS: The follow-up study included 54 hospitalized patients with laboratory-confirmed COVID-19 with a moderate and severe/critical form of the disease. Iron deficiency specific biomarkers such as iron, ferritin, transferrin receptor, hepcidin, and zinc protoporphyrin (ZnPP) as well as relevant markers of inflammation were evaluated twice: in the first five days when the patient was admitted to the hospital and during five to 15 days; and their validity to diagnose iron deficiency was further assessed. The regression and Receiver Operating Characteristics (ROC) analyses were performed to evaluate the prognosis and determine the probability for predicting the severity of the disease in the first five days of COVID-19. RESULTS: Based on hemoglobin values, anemia was observed in 21 of 54 patients. Of all iron deficiency anemia-related markers, only ZnPP was significantly elevated (P<0.001) in the anemic group. When patients were grouped according to the severity of disease, slight differences in hemoglobin or other anemia-related parameters could be observed. However, the levels of ZnPP were significantly increased in the severely ill group of patients. The ratio of ZnPP to lymphocyte count (ZnPP/L) had a discrimination power stronger than the neutrophil to lymphocyte count ratio (N/L) to determine disease severity. Additionally, only two markers were independently associated with the severity of COVID-19 in logistic regression analysis; D-dimer (OR (5.606)(95% CI 1.019-30.867)) and ZnPP/L ratio (OR (74.313) (95% CI 1.081-5108.103)). CONCLUSIONS: For the first time ZnPP in COVID-19 patients were reported in this study. Among all iron-related markers tested, ZnPP was the only one that was associated with anemia as based on hemoglobin. The increase in ZnPP might indicate that the underlying cause of anemia in COVID-19 patients is not only due to the inflammation but also of nutritional origin. Additionally, the ZnPP/L ratio might be a valid prognostic marker for the severity of COVID-19.


Тема - темы
Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/complications , COVID-19/blood , COVID-19/complications , Protoporphyrins/blood , SARS-CoV-2/genetics , Severity of Illness Index , Adult , Aged , Anemia, Iron-Deficiency/epidemiology , Biomarkers/blood , COVID-19/epidemiology , COVID-19/virology , Female , Fibrin Fibrinogen Degradation Products/analysis , Follow-Up Studies , Hemoglobins/analysis , Humans , Logistic Models , Lymphocyte Count , Male , Middle Aged , Patient Admission , Prognosis , Turkey/epidemiology
16.
Eur J Clin Invest ; 52(9): e13827, 2022 Sep.
Статья в английский | MEDLINE | ID: covidwho-1909369

Реферат

BACKGROUND: COVID-19 global pandemic started in late 2019 with the first wave. In this cross-sectional and observational study, we evaluated the associations between the biomarkers, COVID-19 pneumonia severity and 1-year mortality. METHODS: A sample of 276 polymerase chain reaction (PCR)-positive patients for SARS-CoV-2 was included. Computerized tomography severity score (CT-SS) was used to assess the severity of COVID-19 pneumonia in 222 cases. Multivariate analyses were performed to find the predictors of CT-SS, severe CT-SS (≥20) and 1-year mortality. Biomarkers of ferritin, high-sensitive C-reactive protein (CRP), lactate dehydrogenase (LDH), cardiac troponin (cTn), neutrophil-to-lymphocyte ratio (NLR), uric acid (UA) and d-dimer were routinely measured. RESULTS: Severe CT-SS (>20) was observed in 86 (31.2%) cases. Mortality was observed in 75 (27.2%) patients at 1 year. LDH displayed the highest predictive accuracy for severe CT-SS (AUC 0.741, sensitivity = 81% and specificity = 68%, cut-off value: 360 mg/dl). Linear regression analysis displayed that LDH predicted CT-SS [B = 11 (95% CI for B = 5-17, p < .001)]. Age was the most significant parameter that was associated with severe CT-SS (OR 0.96, 95% CI 0.92-0.99, p = .015). d-dimer was the only biomarker that predicted with 1-year mortality (OR 1.62, 95% CI 1.08-2.42, p = .020). CONCLUSION: LDH is a sensitive and specific biomarker to determine patients with severe lung injury in COVID-19. d-dimer is the only biomarker that predicts 1-year mortality. Neither LDH nor CT-SS is associated with 1-year mortality.


Тема - темы
COVID-19 , Lung Injury , Biomarkers/blood , COVID-19/diagnosis , COVID-19/mortality , Cross-Sectional Studies , Fibrin Fibrinogen Degradation Products/analysis , Humans , L-Lactate Dehydrogenase/blood , Lung Injury/virology , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
17.
APMIS ; 130(9): 590-596, 2022 Sep.
Статья в английский | MEDLINE | ID: covidwho-1909331

Реферат

Ferritin, the central iron storage protein, has attracted attention as a biomarker of severe COVID-19. Few studies have investigated regulators of iron metabolism in the context of COVID-19. The aim was to evaluate biomarkers for iron metabolism in the acute phase response to community-acquired pneumonia (CAP) caused by SARS-CoV-2 compared with CAP caused by bacteria or influenza virus in hospitalized patients. A cross-sectional study of 164 patients from the Surviving Pneumonia Cohort recruited between January 8, 2019 and May 26, 2020. Blood samples were collected at admission and analyzed for levels of C-reactive protein (CRP), ferritin, soluble transferrin receptor, erythroferrone, and hepcidin. Median (IQR) hepcidin was higher in SARS-CoV-2 with 143.8 (100.7-180.7) ng/mL compared with bacterial and influenza infection with 78.8 (40.1-125.4) and 53.5 (25.2-125.8) ng/mL, respectively. The median ferritin level was more than 2-fold higher in patients with SARS-CoV-2 compared with the other etiologies (p < 0.001). Patients with SARS-CoV-2 had lower levels of erythroferrone and CRP compared with those infected with bacteria. Higher levels of hepcidin and lower levels of erythroferrone despite lower CRP levels among patients with SARS-CoV-2 compared with those infected with bacteria indicate alterations in iron metabolism in patients with SARS-CoV-2 infection.


Тема - темы
COVID-19 , Community-Acquired Infections , Influenza, Human , Pneumonia, Bacterial , Pneumonia, Viral , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/complications , Community-Acquired Infections/blood , Community-Acquired Infections/diagnosis , Cross-Sectional Studies , Ferritins , Hepcidins/metabolism , Humans , Influenza, Human/complications , Iron/metabolism , Pneumonia, Bacterial/blood , Pneumonia, Bacterial/diagnosis , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , SARS-CoV-2
18.
Front Immunol ; 13: 833310, 2022.
Статья в английский | MEDLINE | ID: covidwho-1902989

Реферат

Immune checkpoints (ICPs) consist of paired receptor-ligand molecules that exert inhibitory or stimulatory effects on immune defense, surveillance, regulation, and self-tolerance. ICPs exist in both membrane and soluble forms in vivo and in vitro. Imbalances between inhibitory and stimulatory membrane-bound ICPs (mICPs) in malignant cells and immune cells in the tumor immune microenvironment (TIME) have been well documented. Blockades of inhibitory mICPs have emerged as an immense breakthrough in cancer therapeutics. However, the origin, structure, production regulation, and biological significance of soluble ICPs (sICPs) in health and disease largely remains elusive. Soluble ICPs can be generated through either alternative mRNA splicing and secretion or protease-mediated shedding from mICPs. Since sICPs are found in the bloodstream, they likely form a circulating immune regulatory system. In fact, there is increasing evidence that sICPs exhibit biological functions including (1) regulation of antibacterial immunity, (2) interaction with their mICP compartments to positively or negatively regulate immune responses, and (3) competition with their mICP compartments for binding to the ICP blocking antibodies, thereby reducing the efficacy of ICP blockade therapies. Here, we summarize current data of sICPs in cancer and infectious diseases. We particularly focus on sICPs in COVID-19 and HIV infection as they are the two ongoing global pandemics and have created the world's most serious public health challenges. A "storm" of sICPs occurs in the peripheral circulation of COVID-19 patients and is associated with the severity of COVID-19. Similarly, sICPs are highly dysregulated in people living with HIV (PLHIV) and some sICPs remain dysregulated in PLHIV on antiretroviral therapy (ART), indicating these sICPs may serve as biomarkers of incomplete immune reconstitution in PLHIV on ART. We reveal that HIV infection in the setting of alcohol misuse exacerbates sICP dysregulation as PLHIV with heavy alcohol consumption have significantly elevated plasma levels of many sICPs. Thus, both stimulatory and inhibitory sICPs are present in the bloodstream of healthy people and their balance can be disrupted under pathophysiological conditions such as cancer, COVID-19, HIV infection, and alcohol misuse. There is an urgent need to study the role of sICPs in immune regulation in health and disease.


Тема - темы
Alcoholism/immunology , COVID-19/immunology , HIV Infections/immunology , HIV-1/physiology , Neoplasms/immunology , SARS-CoV-2/physiology , Biomarkers/blood , Humans , Immune Checkpoint Proteins/blood , Severity of Illness Index
19.
Sci Rep ; 12(1): 640, 2022 01 12.
Статья в английский | MEDLINE | ID: covidwho-1900548

Реферат

COVID-19 pathophysiology is currently not fully understood, reliable prognostic factors remain elusive, and few specific therapeutic strategies have been proposed. In this scenario, availability of biomarkers is a priority. MS-based Proteomics techniques were used to profile the proteome of 81 plasma samples extracted in four consecutive days from 23 hospitalized COVID-19 associated pneumonia patients. Samples from 10 subjects that reached a critical condition during their hospital stay and 10 matched non-severe controls were drawn before the administration of any COVID-19 specific treatment and used to identify potential biomarkers of COVID-19 prognosis. Additionally, we compared the proteome of five patients before and after glucocorticoids and tocilizumab treatment, to assess the changes induced by the therapy on our selected candidates. Forty-two proteins were differentially expressed between patients' evolution groups at 10% FDR. Twelve proteins showed lower levels in critical patients (fold-changes 1.20-3.58), of which OAS3 and COG5 found their expression increased after COVID-19 specific therapy. Most of the 30 proteins over-expressed in critical patients (fold-changes 1.17-4.43) were linked to inflammation, coagulation, lipids metabolism, complement or immunoglobulins, and a third of them decreased their expression after treatment. We propose a set of candidate proteins for biomarkers of COVID-19 prognosis at the time of hospital admission. The study design employed is distinctive from previous works and aimed to optimize the chances of the candidates to be validated in confirmatory studies and, eventually, to play a useful role in the clinical practice.


Тема - темы
Blood Proteins , COVID-19/blood , COVID-19/diagnosis , Hospitalization , Aged , Aged, 80 and over , Biomarkers/blood , Disease Progression , Female , Humans , Male , Mass Spectrometry , Middle Aged , Prospective Studies , Proteome
20.
EBioMedicine ; 76: 103856, 2022 Feb.
Статья в английский | MEDLINE | ID: covidwho-1894987

Реферат

BACKGROUND: Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is nafamostat mesylate. METHODS: We present the findings of a phase Ib/IIa open label, platform randomised controlled trial of intravenous nafamostat in hospitalised patients with confirmed COVID-19 pneumonitis. Patients were assigned randomly to standard of care (SoC), nafamostat or an alternative therapy. Nafamostat was administered as an intravenous infusion at a dose of 0.2 mg/kg/h for a maximum of seven days. The analysis population included those who received any dose of the trial drug and all patients randomised to SoC. The primary outcomes of our trial were the safety and tolerability of intravenous nafamostat as an add on therapy for patients hospitalised with COVID-19 pneumonitis. FINDINGS: Data is reported from 42 patients, 21 of which were randomly assigned to receive intravenous nafamostat. 86% of nafamostat-treated patients experienced at least one AE compared to 57% of the SoC group. The nafamostat group were significantly more likely to experience at least one AE (posterior mean odds ratio 5.17, 95% credible interval (CI) 1.10 - 26.05) and developed significantly higher plasma creatinine levels (posterior mean difference 10.57 micromol/L, 95% CI 2.43-18.92). An average longer hospital stay was observed in nafamostat patients, alongside a lower rate of oxygen free days (rate ratio 0.55-95% CI 0.31-0.99, respectively). There were no other statistically significant differences in endpoints between nafamostat and SoC. PK data demonstrated that intravenous nafamostat was rapidly broken down to inactive metabolites. We observed no significant anticoagulant effects in thromboelastometry. INTERPRETATION: In hospitalised patients with COVID-19, we did not observe evidence of anti-inflammatory, anticoagulant or antiviral activity with intravenous nafamostat, and there were additional adverse events. FUNDING: DEFINE was funded by LifeArc (an independent medical research charity) under the STOPCOVID award to the University of Edinburgh. We also thank the Oxford University COVID-19 Research Response Fund (BRD00230).


Тема - темы
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Benzamidines/therapeutic use , COVID-19/drug therapy , Guanidines/therapeutic use , Administration, Intravenous , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Benzamidines/adverse effects , Benzamidines/pharmacokinetics , Biomarkers/blood , Biomarkers/metabolism , COVID-19/mortality , COVID-19/virology , Drug Administration Schedule , Female , Guanidines/adverse effects , Guanidines/pharmacokinetics , Half-Life , Humans , Immunophenotyping , Kaplan-Meier Estimate , Male , Middle Aged , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Treatment Outcome , Viral Load
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