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1.
Proc Natl Acad Sci U S A ; 119(34): e2201541119, 2022 08 23.
Article in English | MEDLINE | ID: covidwho-1984598

ABSTRACT

Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) ß and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2-specific seroconversion, and enrichment of some shared SARS-CoV-2-associated sequences. No significant age-related or disease severity-related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRß and TCRδ loci, including some TCRß sequence-sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection.


Subject(s)
Adaptive Immunity , COVID-19 , Immunoglobulin Heavy Chains , Receptors, Antigen, T-Cell, alpha-beta , Receptors, Antigen, T-Cell , SARS-CoV-2 , Adaptive Immunity/genetics , Aged , B-Lymphocytes/immunology , COVID-19/genetics , COVID-19/immunology , Genetic Loci , Humans , Immunoglobulin Heavy Chains/genetics , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell, alpha-beta/genetics , SARS-CoV-2/immunology , Seroconversion , T-Lymphocytes/immunology
2.
Applied Soft Computing ; : 108178, 2021.
Article in English | ScienceDirect | ID: covidwho-1549651

ABSTRACT

Research on biomedical science has many components like biomedical engineering, biomedical signal processing, gene analysis, and biomedical image processing. Classification, detection, and recognition have a great value for disease diagnosis and analysis. In this work, biomedical image classification is discussed. In one part, the brain tumor is considered with brain magnetic resonance images and in the other part, COVID affected chest X-rays have been classified using the ensemble approach. The images have been collected from Kaggle online platform. For this purpose, four heterogeneous base classifiers as Convolutional Neural Network, Recurrent Neural Network, Long Short Term Memory, and Gated Recurrent Unit are considered, and metadata is generated. Further, for the detection purpose, a fuzzy min–max model is utilized to avoid uncertainty. The ensemble output from the base classifiers is fed to the fuzzy model in terms of class probability and labels. The min–max algorithm for correct decisions is used in the fuzzy model. The measuring parameters like precision, recall, accuracy, sensitivity, specificity, and F1-score are evaluated. 100% training accuracy for both the datasets is obtained whereas 97.62% and 95.24% of validation accuracy are found for brain image and chest X-ray image classification respectively as exhibited in the result section.

3.
Nat Immunol ; 22(12): 1490-1502, 2021 12.
Article in English | MEDLINE | ID: covidwho-1454796

ABSTRACT

Despite extensive studies into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the effect of maternal infection on the neonate is unclear. To investigate this, we characterized the immunology of neonates born to mothers with confirmed SARS-CoV-2 infection during pregnancy. Here we show that maternal SARS-CoV-2 infection affects the neonatal immune system. Despite similar proportions of B cells, CD4+ T cells and CD8+ T cells, increased percentages of natural killer cells, Vδ2+ γδ T cells and regulatory T cells were detected in neonates born to mothers with recent or ongoing infection compared with those born to recovered or uninfected mothers. Increased plasma cytokine levels were also evident in neonates and mothers within the recent or ongoing infection group. Cytokine functionality was enhanced in neonates born to SARS-CoV-2-exposed mothers, compared to those born to uninfected mothers. In most neonates, this immune imprinting was nonspecific, suggesting vertical transmission of SARS-CoV-2 is limited, a finding supported by a lack of SARS-CoV-2-specific IgM in neonates despite maternal IgG transfer.


Subject(s)
COVID-19/immunology , Infant, Newborn, Diseases/immunology , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Viral/immunology , COVID-19/diagnosis , COVID-19/virology , Cytokines/blood , Cytokines/immunology , Cytokines/metabolism , Female , Humans , Immunity, Innate/immunology , Immunoglobulin G/immunology , Infant, Newborn , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/virology , Killer Cells, Natural/immunology , Pregnancy , Pregnancy Complications, Infectious/virology , Receptors, Antigen, T-Cell, gamma-delta/immunology , Receptors, Antigen, T-Cell, gamma-delta/metabolism , SARS-CoV-2/physiology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes, Regulatory/immunology
4.
J Surg Oncol ; 125(2): 107-112, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1437061

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic was an unforeseen calamity. Sudden disruption of nonemergency services led to disruption of treatment across all specialties. Oncology revolves around the tenet of timely detection and treatment. Disruption of any sort will jeopardize cure rates. The time interval between coronavirus infection and cancer surgery is variable and needs to be tailored to avoid the progression of the disease. METHODS: We analyzed the impact of preoperative coronavirus disease 2019 (COVID-19) infection on the planned cancer surgery, delay, disease progression, and change of intent of treatment from April 1 to May 31, 2021 at a tertiary care center. All preoperative positive patients were retested after 2 weeks and were considered for surgery if the repeat test was negative and asymptomatic. FINDINGS: Our study included 432 preoperative patients of which 91 (21%) were COVID-19 positive. Amongst this cohort, 76% were operated and the morbidity and mortality were comparable to the COVID-19 negative cohort. Around 10% of the COVID-19 positive were lost to follow up and 10% had disease progression and were deemed palliative INTERPRETATION: SARS-CoV-2 infection has adversely impacted cancer care and a 2-week waiting period postinfection seems to be a safe interval in asymptomatic individuals to consider radical cancer surgery.


Subject(s)
COVID-19/epidemiology , Neoplasms/surgery , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , India/epidemiology , Male , Middle Aged , Neoplasms/mortality , Retrospective Studies , Tertiary Care Centers , Young Adult
5.
Bioengineered ; 12(1): 4407-4419, 2021 12.
Article in English | MEDLINE | ID: covidwho-1373615

ABSTRACT

Widespread infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has led to a global pandemic. Currently, various approaches are being taken up to develop vaccines and therapeutics to treat SARS-CoV2 infection. Consequently, the S protein has become an important target protein for developing vaccines and therapeutics against SARS-CoV2. However, the highly infective nature of SARS-CoV2 restricts experimentation with the virus to highly secure BSL3 facilities. The availability of fusion-enabled, nonreplicating, and nonbiohazardous mimics of SARS-CoV2 virus fusion, containing the viral S or S and M protein in their native conformation on mammalian cells, can serve as a useful substitute for studying viral fusion for testing various inhibitors of viral fusion. This would avoid the use of the BSL3 facility for fusion studies required to develop therapeutics. In the present study, we have developed SARS-CoV2 virus fusion mimics (SCFMs) using mammalian cells transfected with constructs coding for S or S and M protein. The fusogenic property of the mimic(s) and their interaction with the functional human ACE2 receptors was confirmed experimentally. We have also shown that such mimics can easily be used in an inhibition assay. These mimic(s) can be easily prepared on a large scale, and such SCFMs can serve as an invaluable resource for viral fusion inhibition assays and in vitro screening of antiviral agents, which can be shared/handled between labs/facilities without worrying about any biohazard while working under routine laboratory conditions, avoiding the use of BSL3 laboratory.Abbreviations :SCFM: SARS-CoV2 Virus Fusion Mimic; ACE2: Angiotensin-Converting Enzyme 2; hACE2: Human Angiotensin-Converting enzyme 2; MEF: Mouse Embryonic Fibroblasts; HBSS: Hanks Balanced Salt Solution; FBS: Fetal Bovine Serum.


Subject(s)
Antibodies, Neutralizing/pharmacology , Containment of Biohazards/methods , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Viral Matrix Proteins/antagonists & inhibitors , Virus Internalization/drug effects , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Chlorocebus aethiops , Embryo, Mammalian , Fibroblasts/drug effects , Fibroblasts/virology , Gene Expression , Genes, Reporter , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , HEK293 Cells , Humans , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , MCF-7 Cells , Mice , Molecular Mimicry , Plasmids/chemistry , Plasmids/metabolism , Primary Cell Culture , Protein Binding , Receptors, Virus/genetics , Receptors, Virus/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Transfection , Vero Cells , Viral Matrix Proteins/genetics , Viral Matrix Proteins/metabolism
6.
Indian J Psychiatry ; 63(1): 112-113, 2021.
Article in English | MEDLINE | ID: covidwho-1110568
8.
Nat Med ; 26(10): 1623-1635, 2020 10.
Article in English | MEDLINE | ID: covidwho-717130

ABSTRACT

Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. Some signature traits identify links with other settings of immunoprotection and immunopathology; others, including basophil and plasmacytoid dendritic cell depletion, correlate strongly with disease severity; while a third set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation in other COVID-19 cohorts, individual traits within this signature may collectively and individually guide treatment options; offer insights into COVID-19 pathogenesis; and aid early, risk-based patient stratification that is particularly beneficial in phasic diseases such as COVID-19.


Subject(s)
Antibodies, Viral/immunology , B-Lymphocytes/immunology , Coronavirus Infections/immunology , Cytokines/immunology , Dendritic Cells/immunology , Pneumonia, Viral/immunology , T-Lymphocytes/immunology , Aged , B-Lymphocyte Subsets/immunology , Basophils/immunology , Betacoronavirus , COVID-19 , Case-Control Studies , Cell Cycle , Chemokine CXCL10/immunology , Chemokines/immunology , Cohort Studies , Coronavirus Infections/blood , Disease Progression , Female , Flow Cytometry , Hospitalization , Humans , Immunologic Memory , Immunophenotyping , Interleukin-10/immunology , Interleukin-6/immunology , Leukocyte Count , Lymphocyte Activation/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Prognosis , SARS-CoV-2 , Severity of Illness Index , T-Lymphocyte Subsets/immunology , Up-Regulation
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