scholarly journals Learning From Biological and Computational Machines: Importance of SARS-CoV-2 Genomic Surveillance, Mutations and Risk Stratification

2021 ◽  
Vol 11 ◽  
Author(s):  
Shikha Bhat ◽  
Anuradha Pandey ◽  
Akshay Kanakan ◽  
Ranjeet Maurya ◽  
Janani Srinivasa Vasudevan ◽  
...  
Keyword(s):  
Severe Disease ◽  
Genomic Analysis ◽  
Physical Symptoms ◽  
Statistical Correlation ◽  
Healthcare Management ◽  
Genomic Diversity ◽  
Total Leukocyte Count ◽  
Diagnostic Parameters ◽  
Reactive Protein ◽  
Roc Score

The global coronavirus disease 2019 (COVID-19) pandemic has demonstrated the range of disease severity and pathogen genomic diversity emanating from a singular virus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2). This diversity in disease manifestations and genomic mutations has challenged healthcare management and resource allocation during the pandemic, especially for countries such as India with a bigger population base. Here, we undertake a combinatorial approach toward scrutinizing the diagnostic and genomic diversity to extract meaningful information from the chaos of COVID-19 in the Indian context. Using methods of statistical correlation, machine learning (ML), and genomic sequencing on a clinically comprehensive patient dataset with corresponding with/without respiratory support samples, we highlight specific significant diagnostic parameters and ML models for assessing the risk of developing severe COVID-19. This information is further contextualized in the backdrop of SARS-CoV-2 genomic features in the cohort for pathogen genomic evolution monitoring. Analysis of the patient demographic features and symptoms revealed that age, breathlessness, and cough were significantly associated with severe disease; at the same time, we found no severe patient reporting absence of physical symptoms. Observing the trends in biochemical/biophysical diagnostic parameters, we noted that the respiratory rate, total leukocyte count (TLC), blood urea levels, and C-reactive protein (CRP) levels were directly correlated with the probability of developing severe disease. Out of five different ML algorithms tested to predict patient severity, the multi-layer perceptron-based model performed the best, with a receiver operating characteristic (ROC) score of 0.96 and an F1 score of 0.791. The SARS-CoV-2 genomic analysis highlighted a set of mutations with global frequency flips and future inculcation into variants of concern (VOCs) and variants of interest (VOIs), which can be further monitored and annotated for functional significance. In summary, our findings highlight the importance of SARS-CoV-2 genomic surveillance and statistical analysis of clinical data to develop a risk assessment ML model.

scholarly journals Serum C-Reactive Protein and Interleukin-6 Levels as Biomarkers for Disease Severity and Clinical Outcomes in Patients with Idiopathic Granulomatous Mastitis

2021 ◽  
Vol 10 (10) ◽  
pp. 2077
Author(s):  
Yi-Min Huang ◽  
Chiao Lo ◽  
Chiao-Feng Cheng ◽  
Cheng-Hsun Lu ◽  
Song-Chou Hsieh ◽  
...  
Keyword(s):  
Disease Severity ◽  
Severe Disease ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
Serum Biomarkers ◽  
Healthy Controls ◽  
Granulomatous Mastitis ◽  
C Reactive Protein ◽  
Idiopathic Granulomatous Mastitis ◽  
Reactive Protein

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease mimicking breast cancer. Limited research has been conducted on the application of serum biomarkers. This study aims to investigate the association of serum biomarkers with disease severity in patients with IGM. From November 2011 to March 2020, medical records of patients with IGM were reviewed. Serum cytokine levels were measured in patients and healthy controls between July 2018 and March 2020. A total of 41 patients with histologically proven IGM were found. Serum interleukin (IL)-6 level was significantly higher in patients with IGM (n = 11) than healthy controls (n = 7). Serum IL-6 and C-reactive protein (CRP) levels were significantly higher in patients with severe disease than mild and moderate disease. Serum IL-6 (Spearman’s ρ = 0.855; p < 0.001) and CRP (Spearman’s ρ = 0.838; p = 0.001) levels were associated with time to resolution. A higher serum CRP level was associated with a longer time to resolution (B = 0.322; p < 0.001) in multiple linear regression analysis. Serum IL-6 and CRP levels can be used as biomarkers for the evaluation of disease severity in IGM. IL-6 may play a crucial role in the immunopathology of IGM.

Oxidative burst and phagocytic activity of phagocytes in canine parvoviral enteritis

2021 ◽  
pp. 104063872110255
Author(s):  
Kelly du Preez ◽  
Yolandi Rautenbach ◽  
Emma H. Hooijberg ◽  
Amelia Goddard
Keyword(s):  
Oxidative Burst ◽  
Phagocytic Activity ◽  
Severe Disease ◽  
Burst Activity ◽  
E Coli ◽  
Reactive Protein ◽  
Oxidative Burst Activity ◽  
Healthy Control ◽  
Complete Blood Counts ◽  
Serum Crp

Canine parvoviral enteritis (CPE) is a severe disease characterized by systemic inflammation and immunosuppression. The function of circulating phagocytes (neutrophils and monocytes) in affected dogs has not been fully investigated. We characterized the functional capacity of canine phagocytes in CPE by determining their oxidative burst and phagocytic activities using flow cytometry. Blood was collected from 28 dogs with CPE and 11 healthy, age-matched, control dogs. Oxidative burst activity was assessed by stimulating phagocytes with opsonized Escherichia coli or phorbol 12-myristate 13-acetate (PMA) and measuring the percentage of phagocytes producing reactive oxygen species and the magnitude of this production. Phagocytosis was measured by incubating phagocytes with opsonized E. coli and measuring the percentage of phagocytes containing E. coli and the number of bacteria per cell. Complete blood counts and serum C-reactive protein (CRP) concentrations were also determined. Serum CRP concentration was negatively and positively correlated with segmented and band neutrophil concentrations, respectively. Overall, no differences in phagocyte function were found between dogs with CPE and healthy control dogs. However, infected dogs with neutropenia or circulating band neutrophils had decreased PMA-stimulated oxidative burst activity compared to healthy controls. Additionally, CPE dogs with neutropenia or circulating band neutrophils had decreased PMA- and E. coli–stimulated oxidative burst activity and decreased phagocytosis of E. coli compared to CPE dogs without neutropenia or band neutrophils. We conclude that phagocytes have decreased oxidative burst and phagocytic activity in neutropenic CPE dogs and in CPE dogs with circulating band neutrophils.

scholarly journals Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Israel Júnior Borges do Nascimento ◽  
Dónal P. O’Mathúna ◽  
Thilo Caspar von Groote ◽  
Hebatullah Mohamed Abdulazeem ◽  
Ishanka Weerasekara ◽  
...  
Keyword(s):  
Systematic Reviews ◽  
Troponin I ◽  
Clinical Symptoms ◽  
Meta Analysis ◽  
Severe Disease ◽  
Ground Glass Opacity ◽  
Cochrane Library ◽  
Reactive Protein ◽  
Overview Of Systematic Reviews ◽  
The Impact

Abstract Background Navigating the rapidly growing body of scientific literature on the SARS-CoV-2 pandemic is challenging, and ongoing critical appraisal of this output is essential. We aimed to summarize and critically appraise systematic reviews of coronavirus disease (COVID-19) in humans that were available at the beginning of the pandemic. Methods Nine databases (Medline, EMBASE, Cochrane Library, CINAHL, Web of Sciences, PDQ-Evidence, WHO’s Global Research, LILACS, and Epistemonikos) were searched from December 1, 2019, to March 24, 2020. Systematic reviews analyzing primary studies of COVID-19 were included. Two authors independently undertook screening, selection, extraction (data on clinical symptoms, prevalence, pharmacological and non-pharmacological interventions, diagnostic test assessment, laboratory, and radiological findings), and quality assessment (AMSTAR 2). A meta-analysis was performed of the prevalence of clinical outcomes. Results Eighteen systematic reviews were included; one was empty (did not identify any relevant study). Using AMSTAR 2, confidence in the results of all 18 reviews was rated as “critically low”. Identified symptoms of COVID-19 were (range values of point estimates): fever (82–95%), cough with or without sputum (58–72%), dyspnea (26–59%), myalgia or muscle fatigue (29–51%), sore throat (10–13%), headache (8–12%) and gastrointestinal complaints (5–9%). Severe symptoms were more common in men. Elevated C-reactive protein and lactate dehydrogenase, and slightly elevated aspartate and alanine aminotransferase, were commonly described. Thrombocytopenia and elevated levels of procalcitonin and cardiac troponin I were associated with severe disease. A frequent finding on chest imaging was uni- or bilateral multilobar ground-glass opacity. A single review investigated the impact of medication (chloroquine) but found no verifiable clinical data. All-cause mortality ranged from 0.3 to 13.9%. Conclusions In this overview of systematic reviews, we analyzed evidence from the first 18 systematic reviews that were published after the emergence of COVID-19. However, confidence in the results of all reviews was “critically low”. Thus, systematic reviews that were published early on in the pandemic were of questionable usefulness. Even during public health emergencies, studies and systematic reviews should adhere to established methodological standards.

scholarly journals Ecophysiology of Freshwater Verrucomicrobia Inferred from Metagenome-Assembled Genomes

mSphere ◽  
2017 ◽  
Vol 2 (5) ◽  
Author(s):  
Shaomei He ◽  
Sarah L. R. Stevens ◽  
Leong-Keat Chan ◽  
Stefan Bertilsson ◽  
Tijana Glavina del Rio ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Potential Role ◽  
Carbon Sources ◽  
Genomic Analysis ◽  
Distribution Patterns ◽  
Eutrophic Lake ◽  
Genomic Diversity ◽  
Extracellular Electron Transfer ◽  
Different Origins ◽  
Encoding Genes

ABSTRACT Freshwater Verrucomicrobia spp. are cosmopolitan in lakes and rivers, and yet their roles and ecophysiology are not well understood, as cultured freshwater Verrucomicrobia spp. are restricted to one subdivision of this phylum. Here, we greatly expanded the known genomic diversity of this freshwater lineage by recovering 19 Verrucomicrobia draft genomes from 184 metagenomes collected from a eutrophic lake and a humic bog across multiple years. Most of these genomes represent the first freshwater representatives of several Verrucomicrobia subdivisions. Genomic analysis revealed Verrucomicrobia to be potential (poly)saccharide degraders and suggested their adaptation to carbon sources of different origins in the two contrasting ecosystems. We identified putative extracellular electron transfer genes and so-called “Planctomycete-specific” cytochrome c-encoding genes and identified their distinct distribution patterns between the lakes/layers. Overall, our analysis greatly advances the understanding of the function, ecophysiology, and distribution of freshwater Verrucomicrobia, while highlighting their potential role in freshwater carbon cycling. Microbes are critical in carbon and nutrient cycling in freshwater ecosystems. Members of the Verrucomicrobia are ubiquitous in such systems, and yet their roles and ecophysiology are not well understood. In this study, we recovered 19 Verrucomicrobia draft genomes by sequencing 184 time-series metagenomes from a eutrophic lake and a humic bog that differ in carbon source and nutrient availabilities. These genomes span four of the seven previously defined Verrucomicrobia subdivisions and greatly expand knowledge of the genomic diversity of freshwater Verrucomicrobia. Genome analysis revealed their potential role as (poly)saccharide degraders in freshwater, uncovered interesting genomic features for this lifestyle, and suggested their adaptation to nutrient availabilities in their environments. Verrucomicrobia populations differ significantly between the two lakes in glycoside hydrolase gene abundance and functional profiles, reflecting the autochthonous and terrestrially derived allochthonous carbon sources of the two ecosystems, respectively. Interestingly, a number of genomes recovered from the bog contained gene clusters that potentially encode a novel porin-multiheme cytochrome c complex and might be involved in extracellular electron transfer in the anoxic humus-rich environment. Notably, most epilimnion genomes have large numbers of so-called “Planctomycete-specific” cytochrome c-encoding genes, which exhibited distribution patterns nearly opposite to those seen with glycoside hydrolase genes, probably associated with the different levels of environmental oxygen availability and carbohydrate complexity between lakes/layers. Overall, the recovered genomes represent a major step toward understanding the role, ecophysiology, and distribution of Verrucomicrobia in freshwater. IMPORTANCE Freshwater Verrucomicrobia spp. are cosmopolitan in lakes and rivers, and yet their roles and ecophysiology are not well understood, as cultured freshwater Verrucomicrobia spp. are restricted to one subdivision of this phylum. Here, we greatly expanded the known genomic diversity of this freshwater lineage by recovering 19 Verrucomicrobia draft genomes from 184 metagenomes collected from a eutrophic lake and a humic bog across multiple years. Most of these genomes represent the first freshwater representatives of several Verrucomicrobia subdivisions. Genomic analysis revealed Verrucomicrobia to be potential (poly)saccharide degraders and suggested their adaptation to carbon sources of different origins in the two contrasting ecosystems. We identified putative extracellular electron transfer genes and so-called “Planctomycete-specific” cytochrome c-encoding genes and identified their distinct distribution patterns between the lakes/layers. Overall, our analysis greatly advances the understanding of the function, ecophysiology, and distribution of freshwater Verrucomicrobia, while highlighting their potential role in freshwater carbon cycling.

Utility of Blood Markers in Early Prediction of Bacteraemia in Acute Febrile Paediatric Patients – An Observational Cohort Study in a Tertiary Care Hospital of North India

2021 ◽  
Vol 8 (28) ◽  
pp. 2526-2531
Author(s):  
Rabindra Bhunia ◽  
Bindu T. Nair ◽  
Vandana Negi
Keyword(s):  
Tertiary Care Hospital ◽  
Leukocyte Count ◽  
Tertiary Care ◽  
North India ◽  
Total Leukocyte Count ◽  
Care Hospital ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Neutrophil Percentage ◽  
Observational Cohort

BACKGROUND Bacteraemia is a common cause of children presenting to the paediatric emergency with acute febrile illness. Blood cultures remain the gold standard for detection of bacteraemia but the positivity is low and also takes time to show positive results. A rapid and reliable biomarker like procalcitonin (PCT), C-reactive protein (CRP), total leucocyte count (TLC), and neutrophil-lymphocyte count ratio (NLCR) can be used to identify febrile children with greater risk for bacteraemia or serious bacterial infections. This would be very helpful to start early treatment of bacteraemia with antibiotics. METHODS The study was an observational cohort study conducted in the Department of Paediatrics of a tertiary care hospital in North India in children between age group 6 months to 12 years presenting with fever of > 100.4° F for 2 - 7 days. Blood samples were sent for PCT, CRP, TLC, NLCR and blood cultures. RESULTS The most sensitive biomarker was total leukocyte count (47.36 %) followed by the neutrophil percentage (26.32 %), C-reactive protein (21.05 %), and procalcitonin (15.79 %). The most specific biomarker was procalcitonin (75.14 %) followed by C-reactive protein (58.56 %), neutrophil percentage (22.65 %) and total leukocyte count (11.05 %). The only biomarker that was statistically significant between the bacteraemia and non-bacteraemia group in the present study was total leukocyte count (P – value < 0.05). CONCLUSIONS The sensitivity and specificity of each single biomarker is low and hence these cannot be used singly to predict bacteraemia. There should be a combination of biomarkers with adequate sensitivity and specificity that can be used to create an algorithm to aid in diagnosis and prognostication. KEYWORDS Procalcitonin, C-Reactive Protein, Blood Culture, Acute Febrile Patient

scholarly journals Early Fever Is Associated With Clinical Outcomes in Patients With Coronavirus Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Feng-ming Ding ◽  
Yun Feng ◽  
Lei Han ◽  
Yan Zhou ◽  
Yong Ji ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Critically Ill ◽  
Symptom Onset ◽  
Critically Ill Patients ◽  
Severe Disease ◽  
Multivariable Analysis ◽  
Reactive Protein ◽  
Increased Temperature ◽  
Kaplan Meier ◽  
Image Improvement

Fever is one of the typical symptoms of coronavirus disease (COVID-19). We aimed to investigate the association between early fever (EF) and clinical outcomes in COVID-19 patients. A total of 1,014 COVID-19 patients at the Leishenshan Hospital were enrolled and classified into the EF and non-EF groups based on whether they had fever within 5 days of symptom onset. Risk factors for clinical outcomes in patients with different levels of disease severity were analyzed using multivariable analyses. Time from symptom onset to symptom alleviation, CT image improvement, and discharge were longer for patients with moderate and severe disease in the EF group than in the non-EF group. Multivariable analysis showed that sex, EF, eosinophil number, C-reactive protein, and IL-6 levels were positively correlated with the time from symptom onset to hospital discharge in moderate cases. The EF patients showed no significant differences in the development of acute respiratory distress syndrome, compared with the non-EF patients. The Kaplan–Meier curve showed no obvious differences in survival between the EF and non-EF patients. However, EF patients with increased temperature showed markedly lower survival than the non-EF patients with increased temperature. EF had no significant impact on the survival of critically ill patients, while an increase in temperature was identified as an independent risk factor. EF appears to be a predictor of longer recovery time in moderate/severe COVID-19 infections. However, its value in predicting mortality needs to be considered for critically ill patients with EF showing increasing temperature.

Evaluation of Microbiologic and Hematologic Parameters and E-Selectin as Early Predictors for Outcome of Neonatal Sepsis

2009 ◽  
Vol 133 (8) ◽  
pp. 1291-1296 ◽  
Author(s):  
Maysaa El Sayed Zaki ◽  
Hesham El Sayed
Keyword(s):  
Neonatal Sepsis ◽  
Neonatal Intensive Care ◽  
Newborn Infants ◽  
Prognostic Indicator ◽  
Diagnostic Value ◽  
Total Leukocyte Count ◽  
C Reactive Protein ◽  
Gram Negative ◽  
Reactive Protein ◽  
Early Predictors

Abstract Context.—Early diagnosis of neonatal sepsis is mandatory. Various markers are used to diagnose the condition. Objective.—To evaluate the diagnostic value of various clinical data and hematologic parameters, such as total leukocyte count, absolute neutrophil count, immature to total neutrophil ratio, and soluble E-selectin (sE-selectin) in identification and outcome of neonatal sepsis. Design.—Newborn infants with a clinical diagnosis of sepsis in the neonatal intensive care unit at Mansoura University Children's Hospital during the period between July 2007 and December 2007 were eligible for study. In addition, 30 healthy neonates were included in the study. Complete hematologic and microbiologic laboratory investigations were performed, and serum E-selectin was measured. Results.—Plasma sE-selectin levels were significantly higher (P &lt; .001) in infected infants (mean [SD], 156.9 [77.0] ng/mL) than in noninfected (mean [SD], 88.8 [47.1] ng/mL) and healthy infants (mean [SD], 8.67 [3.74] ng/ mL). Infants with gram-negative sepsis had higher sE-selectin levels than did those with gram-positive sepsis (P = .04). C-reactive protein was the best laboratory test for diagnosis of neonatal sepsis, with an overall sensitivity and specificity of 86% and 97%, respectively. Performing sE-selectin with C-reactive protein or immature to total ratio tests increased the specificity, but reduced the sensitivity, of the tests for the determination of neonatal sepsis. Plasma sE-selectin levels were higher in nonsurvivors than in survivors (P = .01) and were higher in those with hemodynamic dysfunction than in those without hemodynamic dysfunction (P &lt; .001). Conclusions.—We conclude that plasma sE-selectin levels are elevated in neonatal sepsis. Significant elevation was associated with gram-negative sepsis. Plasma sE-selectin had low diagnostic value when used alone or in combination with other tests; however, it can be used as a prognostic indicator for the outcome of neonatal sepsis.

scholarly journals IgA2 Antibodies against SARS-CoV-2 Correlate with NET Formation and Fatal Outcome in Severely Diseased COVID-19 Patients

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2676
Author(s):  
Léonie A. N. Staats ◽  
Hella Pfeiffer ◽  
Jasmin Knopf ◽  
Aylin Lindemann ◽  
Julia Fürst ◽  
...  
Keyword(s):  
Severe Disease ◽  
Fatal Outcome ◽  
Adaptive Immune Response ◽  
Extracellular Dna ◽  
Neutrophil Extracellular Trap ◽  
Organ Injury ◽  
Reactive Protein ◽  
Patient Groups ◽  
Specific Igg ◽  
Antibody Levels

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to an adaptive immune response in the host and the formation of anti-SARS-CoV-2 specific antibodies. While IgG responses against SARS-CoV-2 have been characterized quite well, less is known about IgA. IgA2 activates immune cells and induces inflammation and neutrophil extracellular trap (NET) formation which may contribute to organ injury and fatal outcome in SARS-CoV-2-infected patients. SARS-CoV-2 spike protein specific antibody levels were measured in plasma samples of 15 noninfected controls and 82 SARS-CoV-2-infected patients with no or mild symptoms, moderate symptoms (hospitalization) or severe disease (intensive care unit, ICU). Antibody levels were compared to levels of C-reactive protein (CRP) and circulating extracellular DNA (ecDNA) as markers for general inflammation and NET formation, respectively. While levels of SARS-CoV-2-specific IgG were similar in all patient groups, IgA2 antibodies were restricted to severe disease and showed the strongest discrimination between nonfatal and fatal outcome in patients with severe SARS-CoV-2 infection. While anti-SARS-CoV-2 IgG and IgA2 levels correlated with CRP levels in severely diseased patients, only anti-SARS-CoV-2 IgA2 correlated with ecDNA. These data suggest that the formation of anti-SARS-CoV-2 IgA2 during SARS-CoV-2 infection is a marker for more severe disease related to NET formation and poor outcome.

scholarly journals Clonal diversity of Haemophilus influenzae carriage isolated from under the age of 6 years children

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Fahimeh Shooraj ◽  
Bahman Mirzaei ◽  
Seyed Fazlollah Mousavi ◽  
Farzaneh Hosseini
Keyword(s):  
Genetic Diversity ◽  
Gel Electrophoresis ◽  
Genomic Analysis ◽  
Clonal Diversity ◽  
Invasive Disease ◽  
Pulsed Field Gel Electrophoresis ◽  
Genomic Diversity ◽  
Biochemical Tests ◽  
Genetic Origin ◽  
Susceptibility Tests

Abstract Objectives Pharyngeal carriers such as H. influenzae seem to constitute the only reservoir and probably the only transmission vehicle of the invasive disease. The aims of this study were to estimate the prevalence of H. influenzae carriage, to characterize antibiotic susceptibility, and to explore genetic diversity of H. influenzae isolates. Sampling was carried out as nasopharynx swabs among children less than 6 years old volunteers. After traditional biochemical tests, isolates were confirmed by targeting omp6 sequence. Following the susceptibility tests, genomic diversity of strains was analyzed by Pulsed-Field Gel Electrophoresis procedure. Results Out of 328 nasopharynx swabs, 73 strains were identified as H. influenzae. Among H. influenzae isolates, resistance to chloramphenicol (42%) and ampicillin (43%) was observed. Levofloxacin is the most effective antibiotic and the least effect belonged to tetracycline. By genomic analysis of selected H. influenza, 28 PFGE patterns were achieved among which 11 patterns included at least 2 strains. All strains clustered into 25 different clones. The dendrogram analysis of the isolated H. influenzae strains showed that some of these strains had a clonal relationship and common genetic origin. According to our results, antibiotic resistance didn’t show any significant correlation with the clonality of strains.

Sign in / Sign up

Export Citation Format

Share Document